A binary module for microbiota-mediated regulation of γδ17 cells, hallmarked by microbiota-driven expression of programmed cell death protein 1.

Little is known about how microbiota regulate innate-like γδ T cells or how these restrict their effector functions within mucosal barriers, where microbiota provide chronic stimulation. Here, we show that microbiota-mediated regulation of γδ17 cells is binary, where microbiota instruct in situ interleukin-17 (IL-17) production and concomitant expression of the inhibitory receptor programmed cell death protein 1 (PD-1). Microbiota-driven expression of PD-1 and IL-17 and preferential adoption of a PD-1high phenotype are conserved for γδ17 cells across multiple mucosal barriers. Importantly, microbiota-driven PD-1 inhibits in situ IL-17 production by mucosa-resident γδ17 effectors, linking microbiota to their simultaneous activation and suppression. We further show the dynamic nature of this microbiota-driven module and define an inflammation-associated activation state for γδ17 cells marked by augmented PD-1, IL-17, and lipid uptake, thus linking the microbiota to dynamic subset-specific activation and metabolic remodeling to support γδ17 effector functions in a microbiota-dense tissue environment.

Repeated intra-articular injections of umbilical cord-derived mesenchymal stem cells for knee osteoarthritis: a phase I, single-arm study.

INTRODUCTION: Stem cell therapy has emerged as an effective treatment for multiple diseases, and some studies also demonstrate that it may be a promising treatment for osteoarthritis (OA). However, few studies have clarified the safety of repeated intra-articular injection of human umbilical cord-derived mesenchymal stem cells (UC-MSCs). To promote its application in treating OA, we conducted an open-label trial to investigate the safety of repeated intra-articular injections of UC-MSCs. METHODS: Fourteen patients with OA (Kellgrene-Lawrence grade 2 or 3) who received repeated intra-articular injections of UC-MSCs were evaluated in three months of follow-up. The primary outcomes were the adverse events, and the second outcomes included visual analog scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) scores and SF-12 quality of life score. RESULTS: A total of 5 of 14 patients (35.7%) experienced transient adverse reactions, which resolved spontaneously. All patients showed some improvement in knee function limitation and pain after receiving stem cell therapy. VAS score 6.0 to 3.5, WOMAC score 26.0 to 8.5, MOCART score 42.0 to 58.0, SF-12 score 39.0 to 46.0. CONCLUSION: Repeated intra-articular injection of UC-MSCs demonstrates safety in treating OA and does not induce serious adverse events. This treatment may transiently improve symptoms in patients with knee OA and may be a potential therapeutic option for OA.

Developmentally programmed early-age skin localization of iNKT cells supports local tissue development and homeostasis.

Skin is exposed to various environmental assaults and undergoes morphological changes immediately after birth. Proper localization and function of immune cells in the skin is crucial for protection and establishment of skin tissue homeostasis. Here we report the discovery of a developmentally programmed process that directs preferential localization of invariant natural killer T (iNKT) cells to the skin for early local homeostatic regulation. We show that iNKT cells are programmed predominantly with a CCR10+ skin-homing phenotype during thymic development in infant and young mice. Early skin localization of iNKT cells is critical for proper commensal bacterial colonization and tissue development. Mechanistically, skin iNKT cells provide a local source of transferrin that regulates iron metabolism in hair follicle progenitor cells and helps hair follicle development. These findings provide molecular insights into the establishment and physiological functions of iNKT cells in the skin during early life.

Burnout, emotional distress and sleep quality among Chinese psychiatric healthcare workers during the COVID-19 pandemic: a follow-up study.

Background: Different from the very early stages of the COVID-19 pandemic, burnout and chronic mental health problems among health care workers (HCWs) has become a challenge. Research is lacking on the relationship between burnout, stress, emotional distress and sleep quality. Methods: The Chinese center has been involved in the Cope-Corona project since the second survey (T2). Named after the project, a total of three cross-sectional surveys were distributed: T2 (February 16-20, 2021), T3 (May 10-14, 2022), and T4 (December 20-24, 2022). Burnout, depression, anxiety, sleep quality, workplace factors and individual resources were measured. Using the T4 data, we conducted structural equation model (SEM) to examine the mediating role of burnout in predicting emotional distress and sleep quality. Results: 96, 124, and 270 HCWs were enrolled at T2, T3, and T4, respectively. In line with the epidemic trends, the level of perceived COVID-19 related risks was significantly higher at T4, while the feeling of health and safety decreased significantly. At T4, the percentages of participants with clinically significant levels of depression and anxiety symptoms were 18.9% (51/270) and 9.3% (25/270), respectively, while 30.4% (82/270) of them reported poor or very poor sleep quality. According to the SEM, individual resources and workplace factors mainly had an indirect effect in predicting depression and anxiety via burnout. However, neither burnout nor stress was a mediator or predictor of sleep quality. Instead, individual resources, positive workplace factors, and younger age had a direct effect in predicting good sleep quality. Conclusion: Measures designed to enhance workplace factors and individual resources should be implemented to improve psychosomatic wellbeing of HCWs.

Workplace factors can predict the stress levels of healthcare workers during the COVID-19 pandemic: First interim results of a multicenter follow-up study.

Background: Research is lacking on the long-term influence of workplace factors on the mental health of health care workers during the COVID-19 pandemic. Methods: We distributed two online surveys to health care workers between May and October 2020 (T1) and between February and April 2021 (T2). Perceived stress, coronavirus-related risks, and workplace factors were measured via self-report questionnaires at both time points. We conducted hierarchical linear regression to investigate the predictive factors for high stress. Results: A total of 2,110 participants from seven countries and 4,240 participants from nine countries were enrolled at T1 and T2, respectively. Among them, 612 participated in both surveys. We called this cohort T1 + T2. High stress was reported in 53.8 and 61.6% of participants at T1 and T2, respectively. In cohort T1 + T2, compared with the baseline, the level of stress rose significantly (6.0 ± 2.9 vs. 6.4 ± 3.1), as did health/safety in the workplace (3.9 ± 0.8 vs. 4.2 ± 0.7). Unfortunately, we did not detect any significant difference concerning support in the workplace. Among all factors at baseline, being older than 35 [ß (95% CI) = -0.92 (-1.45, -0.40)], support [-0.80 (-1.29, -0.32)], and health/safety in the workplace [-0.33 (-0.65, -0.01)] were independent protective factors, while a positive history of mental disorders [0.81 (0.26, 1.37)] and rejection in private life [0.86 (0.48, 1.25)] were risk factors for high stress at T2. Conclusion: To relieve the high stress of health care workers, organizational-level approaches should be implemented, especially measures designed to enhance support, health/safety in the workplace, and to reduce the rejection of the public.

Prognostic Value of UBE2T and Its Correlation with Immune Infiltrates in Lung Adenocarcinoma.

Non-small cell lung cancer has a subtype with a high morbidity and mortality rate called lung adenocarcinoma (LUAD). It is critical to locate reliable prognostic biomarkers for LUAD at this time. Ubiquitin-conjugating enzyme E2T (UBE2T) has been found in numerous malignancies; however, its expression level and potential functions in LUAD are not completely understood at this time. A differentially expressed gene (DEG) screening method was used to identify genes that were expressed differently in 516 samples from LUAD and 59 samples from TCGA datasets. Clinicopathological markers were correlated with UBE2T expression. Using the Kaplan-Meier plotter database, UBE2T was evaluated for its prognostic value in the context of LUAD. In order to examine the importance of independent prognostic factors, both univariable and multivariable Cox regression models were applied. TIMER and CIBERSORT were utilized in order to investigate the connection that exists between UBE2T expression and tumor-infiltrating immune cells. This study collected 578 DEGs in total, as follows: 171 genes were significantly increased, while 408 genes were significantly decreased. We identified 9 survival-related DEGs in LUAD, including ASF1B, CA9, CCNB2, CCNE1, RRM2, SAPCD2, TCN1, TPX2, and UBE2T. Our attention focused on UBE2T, which was highly expressed in LUAD. A correlation was also found between high UBE2T expression and gender, age, advanced clinical stage, and decreased overall survival. In addition, multivariate analysis demonstrated UBE2T expression to be a significant independent diagnostic factor for patients suffering from LUAD. UBE2T was positively correlated with resting T cell CD4+ memory, myeloid dendritic cell resting, mast cell activated, macrophage M2, and B cell plasma, whereas it was negatively correlated with resting T cell CD4+ memory, MDC resting, MDC activated, macrophage M2, and B cell plasma. Overall, high expression levels of UBE2T correlated with poor overall survival in patients with LUAD, and UBE2T was an independent predictor involved in immune infiltration of LUAD. These findings offer fresh perspectives that contribute to our comprehension of the evolution of LUAD.

Cocktail therapy with prednisolone, vincristine and sirolimus for Kasabach­Merritt phenomenon in 10 infants.

Kasabach-Merritt phenomenon (KMP) is a life-threatening condition caused by rare vascular tumors. To reduce drug resistance observed in monotherapy of KMP with prednisone, vincristine (VCR) or sirolimus, the present study evaluated the efficacy and safety of triad therapy in the treatment of KMP. A total of 10 KMP infants managed with prednisolone, VCR and sirolimus in The Second Affiliated Hospital of Xi'an Jiaotong University (Xi'an, China) between April 2017 and August 2021 were retrospectively reviewed. The three female and seven male infants with KMP underwent cocktail therapy with prednisone, VCR and sirolimus. At diagnosis, the infants, aged 49.1±41.0 days, showed laboratory test results with platelet counts 22±15.4x109/l, fibrinogen 81.7±26.9 mg/dl and D-dimer 38649±13443.6 ng/ml. The average maximal diameter of the tumors at diagnosis was 84.5±25.1 mm. KMP risk is increased by large tumors with deep lesions infiltrating the muscle. Platelet counts normalized after a median 10 days (range, 5-69 days) of treatment. With combination therapy maintained for 46.8±24.4 days, ultrasound showed that the thickness of the tumors decreased by 51% from 28.9±12.1 to 13.9±6.2 mm. Neutropenia and gastrointestinal disorders were the most common adverse effects. The present study found that the cocktail therapy with prednisolone, VCR and sirolimus has favorable tolerance and efficacy for life-threatening KMP. Once a stable condition has been achieved, cocktail therapy should be replaced by sirolimus monotherapy to reduce potential side effects.

Delta-like 4-Derived Notch Signals Differentially Regulate Thymic Generation of Skin-Homing CCR10+NK1.1+ Innate Lymphoid Cells at Neonatal and Adult Stages.

The thymus is a primary lymphoid organ for T cell development. Increasing evidence found that the thymus is also an important site for development of innate lymphoid cells (ILCs). ILCs generated in thymi acquire unique homing properties that direct their localization into barrier tissues such as the skin and intestine, where they help local homeostasis. Mechanisms underlying the developmental programming of unique tissue-homing properties of ILCs are poorly understood. We report in this article that thymic stroma-derived Notch signaling is differentially involved in thymic generation of a population of NK1.1+ group 1 ILCs (ILC1s) with the CCR10+ skin-homing property in adult and neonatal mice. We found that thymic generation of CCR10+NK1.1+ ILC1s is increased in T cell-deficient mice at adult, but not neonatal, stages, supporting the notion that a large number of developing T cells interfere with signals required for generation of CCR10+NK1.1+ ILC1s. In an in vitro differentiation assay, increasing Notch signals promotes generation of CCR10+NK1.1+ ILC1s from hematopoietic progenitors. Knockout of the Notch ligand Delta-like 4 in thymic stroma impairs generation of CCR10+NK1.1+ ILC1s in adult thymi, but development of CCR10+NK1.1+ ILC1s in neonatal thymi is less dependent on Delta-like 4-derived Notch signals. Mechanistically, the Notch signaling is required for proper expression of the IL-7R CD127 on thymic NK1.1+ ILC1s, and deficiency of CD127 also impairs thymic generation of CCR10+NK1.1+ ILC1s at adult, but not perinatal, stages. Our findings advanced understanding of regulatory mechanisms of thymic innate lymphocyte development.

The association between the romantic relationships of parents and offspring depressive symptoms: Mediating effects of offspring communication patterns and romantic relationships.

This study investigated a conceptual model by testing how parental romantic relationships influenced the depressive symptoms of grown-up children and whether the constructive communication patterns of grown-up children and romantic relationships played mediation effects within it. A total of 421 Chinese participants were enrolled in the study. The level of depressive symptoms, romantic relationship satisfaction and closeness, couple communication patterns, and parental romantic relationships were measured via self-report questionnaires. According to the results, the structural equation modeling analysis verified that the severity of participants' depressive symptoms was negatively associated with the parental romantic relationship and that the association was mediated by participants' constructive communication patterns and their own romantic relationships. Furthermore, compared with nondepressed participants, depressed participants were less satisfied with their parental romantic relationships, exhibited fewer constructive communication patterns, and were more distant and unsatisfied with current romantic relationships.

Workforce situation of the Chinese mental health care system: results from a cross-sectional study.

BACKGROUND: High-quality mental health services can improve outcomes for people with mental health problems and abate the burden of mental disorders. We sought to identify the challenges the country's mental health system currently faces and the human resource situation related to psychological services and to provide recommendations on how the mental health workforce situation could be addressed in China. METHODS: This study used a cross-sectional survey design. A web-based questionnaire approach and a convenience sampling method were adopted. It was carried out from September 2020 to January 2021 in China, and we finally included 3824 participants in the analysis. Descriptive statistical analysis of the characteristics of the study sample was performed. The risk factors for competence in psychological counseling/psychotherapy were assessed using multiple linear regression analysis. RESULTS: Workforce related to psychotherapy is scarce in China, especially in Western China and community mental health sectors. Psychiatrists (39.1%) and nurses (38.9%) were the main service providers of psychotherapy in psychiatric hospitals, and clinical psychologists (6.9%) and counsellors (5.0%) were seriously scarce in mental health care sectors. A total of 74.2% of respondents had no systematic psychological training, and 68.4 and 69.2% of them had no self-experience and professional supervision, respectively. Compared with clinical psychologists and counselors, psychiatrists and nurses had less training. Systematic psychological training (ß = - 0.88), self-experience (ß = - 0.59) and professional supervision (ß = - 1.26) significantly influenced psychotherapy capacity (P<0.001). CONCLUSIONS: Sustained effort will be required to provide a high-quality, equitably distributed psychotherapy workforce in China, despite challenges for community mental health sectors and western China being likely to continue for some time. Because mental illness is implicated in so many burgeoning social ills, addressing this shortfall could have wide-ranging benefits.

Inhibition of CCL28/CCR10-Mediated eNOS Downregulation Improves Skin Wound Healing in the Obesity-Induced Mouse Model of Type 2 Diabetes.

Chronic, nonhealing skin wounds, such as diabetic foot ulcers (DFUs), are common in patients with type 2 diabetes. Here, we investigated the role of chemokine (C-C motif) ligand 28 (CCL28) and its receptor C-C chemokine receptor type 10 (CCR10) in downregulation of endothelial nitric (NO) oxide synthase (eNOS) in association with delayed skin wound healing in the db/db mouse model of type 2 diabetes. We observed reduced eNOS expression and elevated CCL28/CCR10 levels in dorsal skin of db/db mice and subdermal leg biopsy specimens from human subjects with type 2 diabetes. Further interrogation revealed that overexpression of CCR10 reduced eNOS expression, NO bioavailability, and tube formation of human dermal microvascular endothelial cells (HDMVECs) in vitro, which was recapitulated in mouse dorsal skin. In addition, incubation of HDMVECs with CCL28 led to internalization of the CCR10/eNOS complex and colocalization with lysosome-associated membrane protein 1. Finally, topical application of myristoylated CCR10 binding domain 7 amino acid (Myr-CBD7) peptide prevented CCR10-eNOS interaction and subsequent eNOS downregulation, enhanced eNOS/NO levels, eNOS/VEGF-R2+ microvessel density, and blood perfusion, reduced inflammatory cytokine levels, and importantly, decreased wound healing time in db/db mice. Thus, endothelial cell CCR10 activation in genetically obese mice with type 2 diabetes promotes eNOS depletion and endothelial dysfunction, and targeted disruption of CCR10/eNOS interaction improves wound healing.

CCL27 is a crucial regulator of immune homeostasis of the skin and mucosal tissues.

Abundant immune cells reside in barrier tissues. Understanding the regulation of these cells can yield insights on their roles in tissue homeostasis and inflammation. Here, we report that the chemokine CCL27 is critical for establishment of resident lymphocytes and immune homeostasis in barrier tissues. CCL27 expression is associated with normal skin and hair follicle development independent of commensal bacterial stimulation, indicative of a homeostatic role for the chemokine. Accordingly, in the skin of CCL27-knockout mice, there is a reduced presence and dysregulated localization of T cells that express CCR10, the cognate receptor to CCL27. Besides, CCL27-knockout mice have overreactive skin inflammatory responses in an imiquimod-induced model of psoriasis. Beyond the skin, CCL27-knockout mice have increased infiltration of CCR10+ T cells into lungs and reproductive tracts, the latter of which also exhibit spontaneous inflammation. Our findings demonstrate that CCL27 is critical for immune homeostasis across barrier tissues.

Activation of CD81+ skin ILC2s by cold-sensing TRPM8+ neuron-derived signals maintains cutaneous thermal homeostasis.

As the outermost barrier tissue of the body, the skin harbors a large number of innate lymphoid cells (ILCs) that help maintain local homeostasis in the face of changing environments. How skin-resident ILCs are regulated and function in local homeostatic maintenance is poorly understood. We here report the discovery of a cold-sensing neuron-initiated pathway that activates skin group 2 ILCs (ILC2s) to help maintain thermal homeostasis. In stearoyl-CoA desaturase 1 (SCD1) knockout mice whose skin is defective in heat maintenance, chronic cold stress induced excessive activation of CCR10-CD81+ST2+ skin ILC2s and associated inflammation. Mechanistically, stimulation of the cold-sensing receptor TRPM8 expressed in sensory neurons of the skin led to increased production of IL-18, which, in turn, activated skin ILC2s to promote thermogenesis. Our findings reveal a neuroimmune link that regulates activation of skin ILC2s to support thermal homeostasis and promotes skin inflammation after hyperactivation.

Differential regulation of CD8+ CD86+ Vγ1.1+ γδT cell responses in skin barrier tissue protection and homeostatic maintenance.

Compared to αßT cells, γδT cells are more innate-like and preferentially function as the first line of defense in barrier tissues. Certain populations of γδT cells possess adaptive immune cell properties but their regulation is not well understood. We herein report that while innate-like γδT17 cells dominated in the skin of WT mice, Vγ1.1+ γδT cells with adaptive T cell-like properties predominantly expanded in the skin of TCRß-/- and B2m-/- mice. Commensal bacteria drove expansion of Vγ1.1+ skin γδT cells, functional properties of which correlated with local immune requirements. That is, Vγ1.1+ skin γδT cells in TCRß-/- mice were a heterogeneous population; while Vγ1.1+ skin γδT cells in B2m-/- mice were mostly CD8+ CD86+ cells that had a similar function of CD8+ CD86+ skin αßT cells in supporting local Treg cells. We also found that intrinsic TGF-ß receptor 2-derived signals in skin CD8+ αßT and γδT cells are required for their expression of CD86, a molecule important in supporting skin Treg cells. Our findings reveal broad functional potentials of γδT cells that are coordinately regulated with αßT cells to help maintain local tissue homeostasis.

Influence of incentive mechanism and fit degree on user's environmental behavior-Taking Alipay "Ant Forest" in China as an example.

How to use game elements to motivate users and influence their behavior has become a new research trend, which is vital for enhancing the willingness of potential platform users to participate in environmental protection. This paper aims to analyze the influence of incentive mechanism and fit degree on user's environmental behavior based on the stimulus-organism-response theory and self-determination theory. The questionnaire data of 500 users was collected and the impact of incentives on user's environmental behavior was analyzed by structural equation modeling. The results show that economic, value, and social incentives have a significant impact on user's environmental behavior. Besides, the value and social incentives of "Ant Forest" game platform positively influence user fit (conscious participation, enthusiasm, and platform interaction), but the impact of economic incentive on platform interaction is not statistically significant. From the perspective of user fit, "Ant Forest" game platform can positively promote users to adopt environmental behavior, because it explores users' needs from their perspective to give full play to the role of game incentives on users' environmental behavior. Additionally, this research provides the practical implications for managers exploring the effects of co-creation processes in developing countries and regions.

Biomimetic cell-adhesive ligand-functionalized peptide composite hydrogels maintain stemness of human amniotic mesenchymal stem cells.

In vivo, stem cells reside in a three-dimensional (3D) extracellular microenvironment in which complicated biophysical and biochemical factors regulate their behaviors. Biomimicking of the stem cell-matrix interactions is an ideal approach for controlling the stem cell fate. This study investigates the effects of the incorporation of cell-adhesive ligands in 3D self-assembling peptide hydrogels to modulate stem cell survival, proliferation, maintenance of stemness, and osteogenic differentiation. The results show that the composite hydrogels were non-cytotoxic and effective for maintaining human amniotic mesenchymal stem cell (hAMSC) survival, proliferation and phenotypic characterization. The expression levels of pluripotent markers were also upregulated in the composite hydrogels. Under inductive media conditions, mineral deposition and mRNA expression levels of osteogenic genes of hAMSCs were enhanced. The increasing expression of integrin α- and ß-subunits for hAMSCs indicates that the ligand-integrin interactions may modulate the cell fate for hAMSCs in composite hydrogels.

Coordinated co-migration of CCR10+ antibody-producing B cells with helper T cells for colonic homeostatic regulation.

In the intestine, IgA antibody-secreting B cells (IgA-ASCs) and helper T cells coordinate to maintain local homeostasis while their dysregulation could lead to development of intestinal inflammatory diseases. However, mechanisms underlying the coordinated localization and function of the B and T cells into the intestine, particularly the colon, are poorly understood. We herein report the first evidence that the gut-homing chemokine receptor CCR10+ IgA-ASCs form conjugates with helper T cells, preferentially regulatory T cells, at their differentiation sites of gut-associated lymphoid organs for their coordinated co-localization into the colon to promote local homeostasis. In CCR10-knockout mice, defective migration of IgA-ASCs also resulted in defective T-cell migration and homeostasis, and development of inflammatory symptoms in the colon. Antigen-specific interaction of CCR10+ IgA-ASCs and T cells is crucial for their homeostatic establishment in the colon. On the other hand, in IgA-knockout mice, preferential expansion of CCR10+ IgG1-ASCs with regulatory functions compensated for CCR10+ IgA-ASCs to help maintain colonic homeostasis. The preferential expansion of specific subclasses of CCR10+ IgG-ASCs with regulatory functions was also found in asymptomatic IgA-deficient patients. These findings suggest coordinated cell migration as a novel mechanism underlying localization and function of B and T cells in colonic homeostatic regulation.

The Essential Role of Selenoproteins in the Resolution of Citrobacter rodentium-Induced Intestinal Inflammation.

Enteropathogenic Escherichia coli (EPEC) leads to adverse colonic inflammation associated with poor resolution of inflammation and loss of epithelial integrity. Micronutrient trace element selenium (Se) is incorporated into selenoproteins as the 21st amino acid, selenocysteine (Sec). Previous studies have shown that such an incorporation of Sec into the selenoproteome is key for the anti-inflammatory functions of Se in macrophages and other immune cells. An intriguing mechanism underlying the anti-inflammatory and pro-resolving effects of Se stems from the ability of selenoproteins to skew arachidonic acid metabolism from pro-inflammatory mediators, prostaglandin E2 (PGE2) toward anti-inflammatory mediators derived from PGD2, such as 15-deoxy-Δ12, 14- prostaglandin J2 (15d-PGJ2), via eicosanoid class switching of bioactive lipids. The impact of Se and such an eicosanoid-class switching mechanism was tested in an enteric infection model of gut inflammation by C. rodentium, a murine equivalent of EPEC. C57BL/6 mice deficient in Se (Se-D) experienced higher mortality when compared to those on Se adequate (0.08 ppm Se) and Se supplemented (0.4 ppm Se) diets following infection. Decreased survival was associated with decreased group 3 innate lymphoid cells (ILC3s) and T helper 17 (Th17) cells in colonic lamina propria of Se-D mice along with deceased expression of epithelial barrier protein Zo-1. Inhibition of metabolic inactivation of PGE2 by 15-prostaglandin dehydrogenase blocked the Se-dependent increase in ILC3 and Th17 cells in addition to reducing epithelial barrier integrity, as seen by increased systemic levels of FITC-dextran following oral administration; while 15d-PGJ2 administration in Se-D mice alleviated the effects by increasing ILC3 and Th17 cells. Mice lacking selenoproteins in monocyte/macrophages via the conditional deletion of the tRNA[Sec] showed increased mortality post infection. Our studies indicate a crucial role for dietary Se in the protection against inflammation following enteric infection via immune mechanisms involving epithelial barrier integrity.