Assessing the association between probable posttraumatic stress disorder symptoms and quality of life among emergency service workers using path analysis.

BACKGROUND: Emergency service workers have highly stressful occupations; the stressors encountered can contribute to the development of mental disorders such as depression, anxiety, and posttraumatic stress disorder (PTSD). OBJECTIVE: The present study used a conceptual model and survey to identify variables influencing the association between probable PTSD and quality of life (QOL) in emergency service workers. METHOD: PTSD was assessed using the Impact of Event Scale-Revised. QOL was assessed using the Medical Outcomes Study 36-Item Short-Form Health Survey. Path analysis was used to determine whether stress-coping (Brief Coping Orientation to Problems Experienced [Brief COPE] scores), social support (Multidimensional Scale of Perceived Social Support [MSPSS] scores), and resilience (Connor-Davidson Resilience Scale scores) explain the association between probable PTSD and QOL among 220 emergency service workers in Japan. RESULTS: Impact of Event Scale-Revised scores were significantly positively associated with Brief COPE Active coping scores and significantly negatively associated with MSPSS scores. Brief COPE Active coping and MSPSS scores were significantly positively associated with Connor-Davidson Resilience Scale scores, which were in turn significantly positively associated with Medical Outcomes Study 36-Item Short-Form Health Survey scores. CONCLUSION: Active coping in response to stressful situations is important for maintaining good mental health among emergency service workers. Active coping and social support may strengthen resilience, and resilience may improve QOL. Screening for mental health and QOL should include simultaneous assessment of stress-coping, social support, and resilience. Although the findings of this cross-sectional study are important, it could not confirm a causal relationship between PTSD and QOL.

Dysfunction of sinus macrophages in tumor-bearing host induces resistance to immunotherapy.

Sinus macrophages in draining lymph nodes (DLNs) are involved in anti-tumor immune reactions. CD169 (Sialoadhesin, Siglec-1) is expressed on sinus macrophages and is considered a surrogate marker for the immunostimulatory phenotype of macrophages. In this study, the significance of sinus macrophages in immunotherapy was evaluated using mouse models. Treatment with anti-programmed death-ligand 1 (PD-L1) antibody suppressed the subcutaneous tumor growth of MC38 and E0771 cells but was not effective against MB49 and LLC tumors. Decreased cytotoxic T-lymphocyte (CTL) infiltration in tumor tissues and CD169 expression in sinus macrophages were observed in MB49 and LLC cells compared to corresponding parameters in MC38 and E0771 cells. The anti-tumor effects of the anti-PD-L1 antibody on MC38 and E0771 cells were abolished when sinus macrophages in DLNs were depleted, suggesting that sinus macrophages are involved in the therapeutic effect of the anti-PD-L1 antibody. Naringin activated sinus macrophages. Naringin inhibited tumor growth in MB49- and LLC-bearing mice but did not affect that in MC38- and E0771-bearing mice. The infiltration of CTLs in tumor tissues and their activation were increased by naringin, and this effect was impaired when sinus macrophages were depleted. Combination therapy with naringin and anti-PD-L1 antibody suppressed MB49 tumor growth. In conclusion, CD169-positive sinus macrophages in DLNs are critical for anti-tumor immune responses, and naringin suppresses tumor growth by activating CD169-positive sinus macrophages and anti-tumor CTL responses. The activation status of sinus macrophages has been suggested to differ among tumor models, and this should be investigated in future studies.

Aberrant monocytopoiesis drives granuloma development in sarcoidosis.

In sarcoidosis, granulomas develop in multiple organs including the liver and lungs. Although mechanistic target of rapamycin complex 1 (mTORC1) activation in macrophages drives granuloma development in sarcoidosis by enhancing macrophage proliferation, little is known about the macrophage subsets that proliferate and mature into granuloma macrophages. Here, we show that aberrantly increased monocytopoiesis gives rise to granulomas in a sarcoidosis model, in which Tsc2, a negative regulator of mTORC1, is conditionally deleted in CSF1R-expressing macrophages (Tsc2csf1rΔ mice). In Tsc2csf1rΔ mice, common myeloid progenitors (CMPs), granulocyte-monocyte progenitors (GMPs), common monocyte progenitors / monocyte progenitors (cMoPs / MPs), inducible monocyte progenitors (iMoPs), and Ly6Cint CX3CR1low CD14- immature monocytes (iMOs), but not monocyte-dendritic cell progenitors (MDPs) and common dendritic cell progenitors (CDPs), accumulated and proliferated in the spleen. Consistent with this, monocytes, neutrophils, and neutrophil-like monocytes increased in the spleens of Tsc2csf1rΔ mice, whereas dendritic cells did not. The adoptive transfer of splenic iMOs into wild-type mice gave rise to granulomas in the liver and lungs. In these target organs, iMOs matured into Ly6Chi classical monocytes/macrophages (cMOs). Giant macrophages (gMAs) also accumulated in the liver and lungs, which were similar to granuloma macrophages in expression of cell surface markers such as MerTK and SLAMF7. Furthermore, the gMA-specific genes were expressed in human macrophages from sarcoidosis skin lesions. These results suggest that mTORC1 drives granuloma development by promoting the proliferation of monocyte/neutrophil progenitors and iMOs predominantly in the spleen, and that proliferating iMOs mature into cMOs and then gMAs to give rise to granuloma after migration into the liver and lungs in sarcoidosis.

Identification of small compounds that inhibit multiple myeloma proliferation by targeting c-Maf transcriptional activity.

Multiple myeloma displays the clonal B cell expansion and the overproduction of monoclonal immunoglobulins. Genetic translocations at 14q32, particularly with partners like 16q23, lead to the dysregulation of oncogene expression, including the significant enhancement of c-Maf. This aberrant expression of c-Maf has prompted research into strategies for targeting this transcription factor as a potential therapeutic avenue for multiple myeloma treatment. In this study, we introduce a screening pipeline to test small compounds for their ability to inhibit c-Maf. Using a luciferase indicator driven by the Ccl8 gene promoter, we identified two small compounds that inhibit transcriptional activity of c-Maf. These molecules impede the proliferation of c-Maf-expressing myeloma cells, and repress the expression of c-Maf target genes such as ITGB7 and CCR1. Importantly, these molecules target c-Maf-expressing multiple myeloma cells, but not c-Maf-negative myeloma cells, showing potential for tailoring therapeutic intervention. In conclusion, our screening pipeline is effective to explore leads for a novel c-Maf inhibitor for multiple myeloma therapy.

The early neutrophil-committed progenitors aberrantly differentiate into immunoregulatory monocytes during emergency myelopoiesis.

Inflammatory stimuli cause a state of emergency myelopoiesis leading to neutrophil-like monocyte expansion. However, their function, the committed precursors, or growth factors remain elusive. In this study we find that Ym1+Ly6Chi monocytes, an immunoregulatory entity of neutrophil-like monocytes, arise from progenitors of neutrophil 1 (proNeu1). Granulocyte-colony stimulating factor (G-CSF) favors the production of neutrophil-like monocytes through previously unknown CD81+CX3CR1lo monocyte precursors. GFI1 promotes the differentiation of proNeu2 from proNeu1 at the cost of producing neutrophil-like monocytes. The human counterpart of neutrophil-like monocytes that also expands in response to G-CSF is found in CD14+CD16- monocyte fraction. The human neutrophil-like monocytes are discriminated from CD14+CD16- classical monocytes by CXCR1 expression and the capacity to suppress T cell proliferation. Collectively, our findings suggest that the aberrant expansion of neutrophil-like monocytes under inflammatory conditions is a process conserved between mouse and human, which may be beneficial for the resolution of inflammation.

Improvements in Compassion and Fears of Compassion throughout the COVID-19 Pandemic: A Multinational Study.

During large-scale disasters, social support, caring behaviours, and compassion are shown to protect against poor mental health outcomes. This multi-national study aimed to assess the fluctuations in compassion over time during the COVID-19 pandemic. Respondents (Time 1 n = 4156, Time 2 n = 980, Time 3 n = 825) from 23 countries completed online self-report questionnaires measuring the flows of compassion (i.e., Compassionate Engagement and Action Scales) and fears of compassion toward self and others and from others (i.e., Fears of Compassion Scales) and mental health at three time-points during a 10-month period. The results for the flows of compassion showed that self-compassion increased at Time 3. Compassion for others increased at Time 2 and 3 for the general population, but in contrast, it decreased in health professionals, possibly linked to burnout. Compassion from others did not change in Time 2, but it did increase significantly in Time 3. For fears of compassion, fears of self-compassion reduced over time, fears of compassion for others showed more variation, reducing for the general public but increasing for health professionals, whilst fears of compassion from others did not change over time. Health professionals, those with compassion training, older adults, and women showed greater flows of compassion and lower fears of compassion compared with the general population, those without compassion training, younger adults, and men. These findings highlight that, in a period of shared suffering, people from multiple countries and nationalities show a cumulative improvement in compassion and reduction in fears of compassion, suggesting that, when there is intense suffering, people become more compassionate to self and others and less afraid of, and resistant to, compassion.

Zika virus spreads through infection of lymph node-resident macrophages.

To disseminate through the body, Zika virus (ZIKV) is thought to exploit the mobility of myeloid cells, in particular monocytes and dendritic cells. However, the timing and mechanisms underlying shuttling of the virus by immune cells remains unclear. To understand the early steps in ZIKV transit from the skin, at different time points, we spatially mapped ZIKV infection in lymph nodes (LNs), an intermediary site en route to the blood. Contrary to prevailing hypotheses, migratory immune cells are not required for the virus to reach the LNs or blood. Instead, ZIKV rapidly infects a subset of sessile CD169+ macrophages in the LNs, which release the virus to infect downstream LNs. Infection of CD169+ macrophages alone is sufficient to initiate viremia. Overall, our experiments indicate that macrophages that reside in the LNs contribute to initial ZIKV spread. These studies enhance our understanding of ZIKV dissemination and identify another anatomical site for potential antiviral intervention.

Corrigendum: Moderating effects of striving to avoid inferiority on income and mental health.

[This corrects the article DOI: 10.3389/fpsyg.2022.838991.].

Mental Health of Japanese Workers: Amotivation Mediates Self-Compassion on Mental Health Problems.

Workplace mental health is a cause for concern in many countries. Globally, 78% of the workforce experienced impairment of their mental health in 2020. In Japan, more than half of employees are mentally distressed. Previously, research has identified that self-compassion (i.e., being kind and understanding towards oneself) and work motivation were important to their mental health. However, how these three components relate to each other remains to be elucidated. Accordingly, this study aimed to examine the relationship between mental health problems, self-compassion and work motivation (i.e., intrinsic motivation, extrinsic motivation and amotivation). A cross-sectional design was employed, where 165 Japanese workers completed self-report scales regarding those three components. A correlation and path analyses were conducted. Mental health problems were positively associated with amotivation and negatively associated with age and self-compassion. While intrinsic motivation and extrinsic motivation did not mediate the impact of self-compassion on mental health problems, amotivation did. The findings can help managers and organizational psychologists help identify effective approaches to improving work mental health.

Benefits of group compassion-focused therapy for treatment-resistant depression: A pilot randomized controlled trial.

Major depression is one of the most common mental health problems worldwide. More than one-third of patients suffer from treatment-resistant depression (TRD). In this study, we explored the feasibility of group compassion-focused therapy (CFT) for TRD using a randomized controlled trial with two parallel groups. Eighteen participants were randomly allocated to the intervention group (CFT and usual care) and control group (usual care alone) and a participant in each group withdrew. Participants in the intervention group received a 1.5-h session every week for 12 weeks. The effects of the intervention on the participants' scores were calculated using a linear mixed model. There was a larger reduction in their depressive symptoms and fears of compassion for self and a greater increase in their compassion for self compared to the control group participants. The reliable clinical indices showed that in the CFT (intervention) group, three of nine participants recovered (33%), two improved (22%), two recovered but non-reliably (22%), and the condition of two remained unchanged (22%). These findings indicate adequate feasibility of group CFT for TRD in Japanese clinical settings. Clinical trial registration: [https://clinicaltrials.gov/], identifier [UMIN 000028698].

Moderating Effects of Striving to Avoid Inferiority on Income and Mental Health.

Many people experience feelings of inferiority in their life. The concept of striving to avoid inferiority is a belief associated with the unwanted fear of being overlooked, missing out on opportunities for advancement, and active rejection. This study examined the effect of striving to avoid inferiority on mental health and well-being. We hypothesized that striving to avoid inferiority would modify the relationship among socioeconomic status, mental health, and well-being, therefore examined the effect of striving to avoid inferiority on the relationship between annual income, mental health, and well-being. The participants were 491 adults (241 men and 250 women). The results indicated that insecure striving (IS) in competition with others positively correlated with depression, anxiety, and stress, whereas secure non-striving (SNS) in acceptance of inferiority positively correlated with the satisfaction with life and negatively correlated with depression. The effect of striving to avoid inferiority on the relationship among annual income, mental health, and well-being indicated that SNS affected the relationships between annual income and well-being, annual income and depression, income and anxiety, and the interaction between IS and SNS. Moreover, the relationship between income and stress was influenced by SNS and the interaction between IS and SNS. These results indicated that SNS or the interaction between IS and SNS were the only variables regulating the relationship among annual income, mental health, and well-being. These findings suggested that accepting feelings of inferiority or striving to avoid inferiority influences the mental health and well-being of people.

The mediating effect of symptoms of posttraumatic stress disorder and depression on the relationship between personality traits and quality of life in emergency service workers.

BACKGROUND: Emergency service workers are often exposed to fatalities during accidents or disasters. Therefore, they may be more prone to experiencing posttraumatic stress disorder (PTSD) and depression. It has been shown that these comorbid disorders are related to personality traits and quality of life (QOL). METHODS: We hypothesized that mental disorders, such as symptoms of PTSD and depression, mediate the relationship between personality traits, as measured on the 10-Item Personality Inventory (TIPI), and QOL, as measured on the MOS 36-item Short-Form Health Survey (SF-36). RESULTS: Participants were aged 23-61 years. Questionnaires were sent to 373 participants, 220 of whom returned responses. A direct effect was found between two subscales of the TIPI (Extraversion and Emotional stability) and mental component summary scores of the SF-36 (Extraversion: ß = 0.154, p < .001; Emotional stability: ß = 0.179, p < .001), which indicated partial mediation. A significant indirect effect was revealed between two personality traits and mental health summary scores (Extraversion: ß = 0.058, p < .001; Emotional stability: ß = 0.087, p < .001). We also found a direct effect of extraversion scores of the TIPI on role/social component summary scores of the SF-36 (ß = 0.084, p < .05). However, none of the 95% confidential intervals was significant, which indicated full mediation, and the indirect effect was significant (ß = 0.023, p < .01). Sensitivity analysis indicated that a direct effect between extraversion scores of the TIPI and role/social component summary scores of the SF-36 was significant, which indicated partial mediation. CONCLUSIONS: The findings of direct and indirect effects highlight the importance of identifying effective methods for protecting individuals from developing symptoms of PTSD and depression; moreover, they may help improve QOL. The capacity of dealing with incidents among emergency service workers may vary depending on their personality traits. Therefore, the screening of mental health states that includes a personality trait inventory may be valuable.

Synaptic pruning of murine adult-born neurons by microglia depends on phosphatidylserine.

New neurons, continuously added in the adult olfactory bulb (OB) and hippocampus, are involved in information processing in neural circuits. Here, we show that synaptic pruning of adult-born neurons by microglia depends on phosphatidylserine (PS), whose exposure on dendritic spines is inversely correlated with their input activity. To study the role of PS in spine pruning by microglia in vivo, we developed an inducible transgenic mouse line, in which the exposed PS is masked by a dominant-negative form of milk fat globule-EGF-factor 8 (MFG-E8), MFG-E8D89E. In this transgenic mouse, the spine pruning of adult-born neurons by microglia is impaired in the OB and hippocampus. Furthermore, the electrophysiological properties of these adult-born neurons are altered in MFG-E8D89E mice. These data suggest that PS is involved in the microglial spine pruning and the functional maturation of adult-born neurons. The MFG-E8D89E-based genetic approach shown in this study has broad applications for understanding the biology of PS-mediated phagocytosis in vivo.

Compassion Protects Mental Health and Social Safeness During the COVID-19 Pandemic Across 21 Countries.

Objectives: The COVID-19 pandemic is having an unprecedented detrimental impact on mental health in people around the world. It is important therefore to explore factors that may buffer or accentuate the risk of mental health problems in this context. Given that compassion has numerous benefits for mental health, emotion regulation, and social relationships, this study examines the buffering effects of different flows of compassion (for self, for others, from others) against the impact of perceived threat of COVID-19 on depression, anxiety, and stress, and social safeness. Methods: The study was conducted in a sample of 4057 adult participants from the general community population, collected across 21 countries from Europe, Middle East, North America, South America, Asia, and Oceania. Participants completed self-report measures of perceived threat of COVID-19, compassion (for self, for others, from others), depression, anxiety, stress, and social safeness. Results: Perceived threat of COVID-19 was associated with higher scores in depression, anxiety, and stress, and lower scores in social safeness. Self-compassion and compassion from others were associated with lower psychological distress and higher social safeness. Compassion for others was associated with lower depressive symptoms. Self-compassion moderated the relationship between perceived threat of COVID-19 on depression, anxiety, and stress, whereas compassion from others moderated the effects of fears of contracting COVID-19 on social safeness. These effects were consistent across all countries. Conclusions: Our findings highlight the universal protective role of compassion, in particular self-compassion and compassion from others, in promoting resilience by buffering against the harmful effects of the COVID-19 pandemic on mental health and social safeness. Supplementary Information: The online version contains supplementary material available at 10.1007/s12671-021-01822-2.

CD169+ macrophages in lymph node and spleen critically depend on dual RANK and LTbetaR signaling.

CD169+ macrophages reside in lymph node (LN) and spleen and play an important role in the immune defense against pathogens. As resident macrophages, they are responsive to environmental cues to shape their tissue-specific identity. We have previously shown that LN CD169+ macrophages require RANKL for formation of their niche and their differentiation. Here, we demonstrate that they are also dependent on direct lymphotoxin beta (LTß) receptor (R) signaling. In the absence or the reduced expression of either RANK or LTßR, their differentiation is perturbed, generating myeloid cells expressing SIGN-R1 in LNs. Conditions of combined haploinsufficiencies of RANK and LTßR revealed that both receptors contribute equally to LN CD169+ macrophage differentiation. In the spleen, the Cd169-directed ablation of either receptor results in a selective loss of marginal metallophilic macrophages (MMMs). Using a RANKL reporter mouse, we identify splenic marginal zone stromal cells as a source of RANKL and demonstrate that it participates in MMM differentiation. The loss of MMMs had no effect on the splenic B cell compartments but compromised viral capture and the expansion of virus-specific CD8+ T cells. Taken together, the data provide evidence that CD169+ macrophage differentiation in LN and spleen requires dual signals from LTßR and RANK with implications for the immune response.

CD169-positive macrophages enhance abscopal effect of radiofrequency ablation therapy in liver cancer.

Radiofrequency ablation (RFA) is a widely used and effective treatment for primary or metastatic liver cancer with small-size lesions. However, the therapeutic effectiveness of RFA in controlling metastatic lesion or recurrence is still limited. As the major cell population in tumor microenvironment (TME), macrophages have been reported to be recruited to RFA-treated lesion, but their roles are still unclear. Herein, we successfully established the mouse model mimicking RFA-induced abscopal effect, in which RFA eliminated the local orthotopic liver tumor but failed to control growth of distant tumor. Correspondently, RFA suppressed protumoral activation of local tumor-associated macrophages (TAMs), but failed to reprogram TAMs in distance. Importantly, although RFA led to reduced proportion of hepatic CD169+ macrophages in local and decreased expression of immune inhibitory molecules Tim-3 and PD-L1, these alterations were not observed for CD169+ macrophages in distant TME. Further RNA-seq and flow cytometry analysis showed that hepatic CD169+ macrophages contributed to reprograming TME through recruiting CD8+ T/NK cells and suppressing accumulation of MDSCs/Tregs. Consistently, depletion of CD169+ macrophages in CD169-DTR mouse greatly promoted liver tumor progression and largely dampened RFA-induced tumor suppression. Notably, transfer of CD169+ macrophages synergistically enhanced RFA-induced inhibition of distant tumor. To our knowledge, this is the first study which demonstrates hepatic CD169+ macrophages as a key factor responsible for RFA-induced abscopal effect. Our data suggest RFA with transfer of CD169+ macrophages as a promising combination therapy to lessen metastasis or recurrence of liver cancer in patients.

The role of social connection on the experience of COVID-19 related post-traumatic growth and stress.

BACKGROUND: Historically social connection has been an important way through which humans have coped with large-scale threatening events. In the context of the COVID-19 pandemic, lockdowns have deprived people of major sources of social support and coping, with others representing threats. Hence, a major stressor during the pandemic has been a sense of social disconnection and loneliness. This study explores how people's experience of compassion and feeling socially safe and connected, in contrast to feeling socially disconnected, lonely and fearful of compassion, effects the impact of perceived threat of COVID-19 on post-traumatic growth and post-traumatic stress. METHODS: Adult participants from the general population (N = 4057) across 21 countries worldwide, completed self-report measures of social connection (compassion for self, from others, for others; social safeness), social disconnection (fears of compassion for self, from others, for others; loneliness), perceived threat of COVID-19, post-traumatic growth and traumatic stress. RESULTS: Perceived threat of COVID-19 predicted increased post-traumatic growth and traumatic stress. Social connection (compassion and social safeness) predicted higher post-traumatic growth and traumatic stress, whereas social disconnection (fears of compassion and loneliness) predicted increased traumatic symptoms only. Social connection heightened the impact of perceived threat of COVID-19 on post-traumatic growth, while social disconnection weakened this impact. Social disconnection magnified the impact of the perceived threat of COVID-19 on traumatic stress. These effects were consistent across all countries. CONCLUSIONS: Social connection is key to how people adapt and cope with the worldwide COVID-19 crisis and may facilitate post-traumatic growth in the context of the threat experienced during the pandemic. In contrast, social disconnection increases vulnerability to develop post-traumatic stress in this threatening context. Public health and Government organizations could implement interventions to foster compassion and feelings of social safeness and reduce experiences of social disconnection, thus promoting growth, resilience and mental wellbeing during and following the pandemic.

Development of the external and internal shame scale: Japanese version.

OBJECTIVE: Shame contains external and internal aspects. However, a Japanese language scale for simultaneously assessing both aspects of shame has not been developed to date. This study aimed to standardize the Japanese version of the External and Internal Shame Scale (EISS-J). An online survey was conducted among university students (N = 203) at six universities in Japan (Study 1). A retest questionnaire was sent to the participants by email three weeks after the first survey (Study 2). Study 1 examined the internal consistency, factor structure, and criterion-related validity of the EISS-J, while Study 2 examined its test-retest reliability. Moreover, an additional study was conducted to examine the criterion-related validity of the scale. RESULTS: Study 1 demonstrated the high internal consistency of the EISS-J. Moreover, confirmatory factor analysis indicated a two-factor model: external and internal shame. However, exploratory factor analysis indicated a three-factor structure. Study 2 confirmed the test-retest reliability of the scale. Furthermore, both studies indicated correlations between the EISS-J and fear of compassion, anger, humiliation, depression, anxiety, and stress. In addition, the study established the criterion-related validity of the scale. These results confirmed adequate reliability and validity of the EISS-J.

Pathogenic roles and therapeutic potential of the CCL8-CCR8 axis in a murine model of IgG4-related sialadenitis.

BACKGROUND: Our previous studies reveal that CCL18-CCR8 chemokine axis is upregulated in patients of immunoglobulin G4-related disease (IgG4-RD), suggesting that the CCL18-CCR8 axis is implicated in the etiology of IgG4-RD, although whether this axis has a potential as a therapeutic target remains unclear. Our purpose was to clarify the pathogenic roles and therapeutic potential of the murine CCL8 (analog of human CCL18)-CCR8 axis by using an animal model of IgG4-RD (LAT Y136F knockin mice; LAT mice). METHODS: We compared the infiltration of inflammatory cells and the fibrosis of the salivary glands of 6-week-old LAT mice and littermate mice. The expressions of Ccl8 and Ccr8 were also compared. Next, we investigated the therapeutic effects of intravenous administration of anti-CCL8 neutralizing antibody in LAT mice against inflammation and fibrosis of the salivary glands. We also investigated the effects of stimulation with recombinant mouse CCL8 on the collagen production in a mouse fibroblast cell line (NIH/3 T3) in vitro. RESULTS: When compared with the littermates, the LAT mice showed apparent infiltration of inflammatory cells and fibrosis in the salivary glands. The focus and fibrosis score in the salivary glands were significantly higher in the LAT mice than in the littermates. The expression levels of Ccl8 in the spleen and of Ccr8 in the salivary glands were significantly higher in the LAT mice than in the littermates. Anti-CCL8 antibody significantly improved the focus and fibrosis score in the salivary glands of the LAT mice. In vitro, stimulation with recombinant mouse CCL8 significantly increased the expression of collagen and ERK1/2 phosphorylation in NIH/3 T3. CONCLUSION: We clarified the overexpression and therapeutic potential of the mouse CCL8-CCR8 axis in LAT mice, which could play a crucial role in fibrosis via ERK1/2 phosphorylation, as well as the chemotaxis of inflammatory cells. The human CCL18-CCR8 axis might be a novel therapeutic target for IgG4-RD.

Replication of Influenza A Virus in Secondary Lymphatic Tissue Contributes to Innate Immune Activation.

The replication of viruses in secondary lymphoid organs guarantees sufficient amounts of pattern-recognition receptor ligands and antigens to activate the innate and adaptive immune system. Viruses with broad cell tropism usually replicate in lymphoid organs; however, whether a virus with a narrow tropism relies on replication in the secondary lymphoid organs to activate the immune system remains not well studied. In this study, we used the artificial intravenous route of infection to determine whether Influenza A virus (IAV) replication can occur in secondary lymphatic organs (SLO) and whether such replication correlates with innate immune activation. Indeed, we found that IAV replicates in secondary lymphatic tissue. IAV replication was dependent on the expression of Sialic acid residues in antigen-presenting cells and on the expression of the interferon-inhibitor UBP43 (Usp18). The replication of IAV correlated with innate immune activation, resulting in IAV eradication. The genetic deletion of Usp18 curbed IAV replication and limited innate immune activation. In conclusion, we found that IAV replicates in SLO, a mechanism which allows innate immune activation.