MMP2hi Fibroblasts Regulate CD8+ T Cell Residency and Inflammation via CD100 in Psoriasis.

BACKGROUND: Psoriasis, a T cell-mediated chronic inflammatory skin condition, is characterized by the interaction of T cells with various cell types, forming an inflammatory microenvironment that sustains psoriatic inflammation. The homeostasis of these tissue-resident T cells are supported by fibroblasts, the primary structural cells in the dermis. In psoriasis, there is an increased expression of matrix metalloproteinase 2 (MMP2), mediating the structural alterations of skin tissues and the modulation of inflammation. Additionally, the CD100-PLXNB2 axis is known to enhance psoriasis inflammation via keratinocytes, and CD103 levels are associated with the severity of psoriasis upon relapse. OBJECTIVE: To elucidate the role of fibroblasts and the MMP2/CD100 axis in modulating psoriasis inflammation. METHODS: CD100 expression and function in psoriasis were assessed using immunofluorescence, ELISA, single-cell transcriptome sequencing, cellular interaction analyses, and qRT-PCR. CD8+ T cells from psoriasis patients were isolated using magnetic beads to investigate the regulatory effect of MMP2 on CD100 expression on their membranes. Single-cell transcriptome sequencing, spatial transcriptome sequencing, mimetic timing analysis, immunofluorescence, and flow cytometry were utilized to determine the origin of MMP2 and its impact on CD103+CD8+ T cells. The hypotheses were further validated in vivo using MMP2 and CD100 inhibitors. RESULTS: Soluble CD100 (sCD100) was significantly upregulated in both psoriatic lesions and peripheral blood, amplifying psoriasis inflammation by promoting the production of inflammatory cytokines by keratinocytes, fibroblasts, and endothelial cells through the sCD100-PLXNB2 axis. Fibroblasts with high MMP2 expression (MMP2hi) exacerbate psoriasis symptoms by facilitating CD100 shedding from CD8+ T cell membranes. Additionally, it was demonstrated that fibroblasts enhance the upregulation of the CD8+ T cell residency factor CD103 in co-cultures with CD8+ T cells. Inhibitors targeting MMP2 and CD100 proved effective in reducing inflammation in a model of imiquimod-induced psoriasis. CONCLUSION: Our findings underscore the pivotal role of MMP2hi fibroblasts in the amplification and recurrence of inflammatory responses in psoriasis. These fibroblasts augment psoriasis inflammation through the CD100-PLXNB2 axis by facilitating CD100 shedding on CD8+ T cell membranes and by upregulating CD103, thereby enhancing CD8+ T cell residency.

LncRNA AGXT2L1-2:2 facilitates keratinocytes proliferation and inhibits apoptosis by interacting with estrogen-related receptor alpha in psoriasis.

Our previous studies have revealed that long noncoding RNA (lncRNA) AGXT2L1-2:2 was highly expressed in keratinocytes of psoriasis. However, the functions of lnc-AGXT2L1-2:2 in keratinocytes remain unknown. Meanwhile, co-expression network analysis indicated lnc-AGXT2L1-2:2 could interact with estrogen-related receptor alpha (ERRα). In this study, interleukin (IL)-17A could stimulate the production of lnc-AGXT2L1-2:2 in keratinocytes, thus establishing an in vitro cellular model of psoriasis. Lnc-AGXT2L1-2:2 was overexpressed using lentiviral-vector and ERRα was downregulated with small interfering RNA. Then the effects of lnc-AGXT2L1-2:2 and ERRα on viability, apoptosis, and cell cycle in IL-17A-stimulated keratinocytes were assessed by CCK-8, EdU assay, and flow cytometry. We found that lnc-AGXT2L1-2:2 and ERRα both resulted in higher proliferation ability, lower apoptosis rates, and reduction of G0/G1 phase proportion. Furthermore, lnc-AGXT2L1-2:2 could promote the expression of ERRα and siERRα antagonized the effects of lnc-AGXT2L1-2:2 on the phenotypes above in IL-17A-induced keratinocytes. In conclusion, lnc-AGXT2L1-2:2 was found to promote keratinocytes proliferation, inhibit cell apoptosis and the effects of lnc-AGXT2L1-2:2 on keratinocytes are dependent on ERRα.

Characteristics and sources of tissue-resident memory T cells in psoriasis relapse.

Tissue-resident memory T cells (Trm) are a sub-population of memory T cells that reside in skin tissue. Recent studies have revealed potential role of Trm in the reoccurrence of psoriasis, as these cells tend to be profusely infiltrated in the lesions observed during psoriasis relapse. Trm can be classified into CD8+ Trm cells that are distributed mainly in the epidermis and CD4+ Trm cells in the dermis. CD8+ Trm is derived from circulating memory T cells and CD49a-CD8+ Trm takes a crucial role in psoriasis relapse. In contrast, CD4+ Trm may originate from exTh17 cells and exTreg cells emerging from the inflammatory process. Since IL-23 can activate Trm, neutralizing antibodies against IL-23 are suggested to be more effective in clinical treatment. This review will focus on Trm cells in psoriasis relapsed lesions to reveal their mechanisms in the pathogenesis, relapse and transformation of psoriasis.

Analysis of Adverse Reactions of Cosmetics in Chinese Han Population in Recent Five Years.

Background: There are still some gaps in the summary and generalization of cosmetic-related adverse reaction reports. Objective: The aim of this study is to summarize and analyze the occurrence of cosmetic adverse reactions in Shanghai Han population by using available survey data. Materials and Methods: Collection, statistics and analysis of patients with cosmetic adverse reactions in Shanghai Huashan Hospital from 2017 to 2021. Results: Among the 1004 patients, most of them (96.71%) were diagnosed as cosmetic contact dermatitis, which often occurred within 3 days of using cosmetics (51.79%). A total of 260 patients were tested with patch test, but the compliance rate was only 18.08%. Among them, 240 patients underwent additional European standard allergen tests, and positive allergens were detected in 210 cases (87.5%). Univariate analysis revealed that dosage form (emulsion and cream), age (≤25 years) and the allergic ingredients triethanolamine, rose oil, propylene glycol, thiomersal and musk ambrette are associated with the occurrence of cosmetic adverse reactions within seven days. A logit prediction model was also successfully constructed: Logit (P) = 1.710-0.796×1 + 1.185×2 -3.650X3-1.335X4. Conclusion: This study complements the data reported on cosmetic adverse reactions in the Chinese Han population and suggests that in future clinical diagnosis and data collection, emphasis should be placed on patch testing, combining the patch test with cosmetic protoplast with the European standard allergen test to improve the detection rate.

The Inflammatory Factor SNP May Serve as a Promising Biomarker for Acitretin to Alleviate Secondary Failure of Response to TNF-a Monoclonal Antibodies in Psoriasis.

Psoriasis is a common immune-mediated inflammatory skin disease. Although biological agents have achieved good clinical efficacy in the treatment of moderate-to-severe psoriasis, the phenomenon of secondary non-response (SNR) has been gradually recognized. SNR refers to the gradual decline of efficacy after the patient achieves clinical remission with biological agents such as TNF-α biologics. Acitretin, as an immunomodulatory systemic drug for psoriasis, can improve the SNR to biological agents with good tolerance, but there are still individual differences in efficacy. Single-nucleotide polymorphisms (SNPs) of many related inflammatory cytokines have been shown to be important factors of individual differences in drug response in psoriasis, but there have been few reports on the use of pharmacogenomics to alleviate the SNR to biological agents. This study recruited 43 patients with psoriasis and 24 normal controls to investigate whether SNPs of inflammatory cytokines could be used as biomarkers for acitretin to alleviate SNR to TNF-α biologics in psoriasis, including rs1800795 (IL-6), rs6887695 (IL-12b), rs3212227 (IL-12b), rs10484879 (IL-17a), rs4819554 (IL-17ra), rs763780 (IL-17F), rs11209032 (IL23R), rs11209026 (IL23R), and rs2201841 (IL23R). The study also analyzed the correlation between the abovementioned SNPs and the efficacy of acitretin-only patients so as to understand whether the improvement is attributable to the intervention of acitretin on SNR or a simple response of acitretin. We found that in patients with homozygous AA (χ2 = 6.577, p = 0.02) at the SNP rs112009032 (IL-23R), acitretin could improve the SNR to TNFα monoclonal antibody. Patients with the genotype of TG (χ2 = 6.124, p = 0.035) at rs3212227 (IL-12B) were more sensitive to using acitretin in the treatment of psoriasis. Rs3212227 (χ2 = 7.664, p = 0.022) was also associated with the susceptibility to psoriasis. The study might provide a clinical decision reference for personalized treatment of secondary loss of response to psoriasis biologics.

Relationship between Different Psoriasis Types and Thyroid Dysfunction: A Retrospective Analysis.

OBJECTIVE: The aim of this study was to investigate the relationship between different psoriasis types and thyroid dysfunction. METHODS: The data of patients diagnosed with psoriasis between January 2013 and October 2018 who underwent thyroid function tests were collected. Free triiodothyronine (FT3), free thyroxine (FT4), total triiodothyronine (TT3), total thyroxine (TT4), thyroid-stimulating hormone (TSH), thyroglobulin antibody (TGAb), and thyroid peroxidase antibody (TPOAb) were measured. The thyroid function of patients with psoriasis vulgaris, pustular psoriasis, erythrodermic psoriasis, and psoriatic arthritis was evaluated, and the differences in hormone levels and antibodies in the pituitary-thyroid axis with psoriasis type were analyzed. RESULTS: The data of a total of 468 patients were analyzed in this study. The proportion of normal hormone levels was higher among vulgaris patients (P < 0.001), while the erythrodermic patients were more likely to have decreased FT3 or FT4 but normal TSH (P < 0.001). FT3 levels were lower in pustular patients (P < 0.05), FT4 levels were lower in erythrodermic patients (P < 0.05), and TSH levels were higher in patients with psoriatic arthritis (P < 0.05). TPOAb levels were higher than normal in all patients, but there was no significant difference in the levels of TPOAb and TGAb among 4 types of the patients. CONCLUSION: Psoriasis is related to thyroid dysfunction, especially in patients with atypical psoriasis types. The possibility of complications should be considered in erythrodermic patients.

Prevalence of Metabolic Syndrome in Chinese Patients With Erythrodermic Psoriasis: A Case-Control Study.

Erythroderma psoriasis (EP) is a rare and severe form of psoriasis, which is a chronic inflammatory skin disease that usually occurs simultaneously with cardiovascular disease (CVD). Metabolic syndrome (MetS) is a significant precursor of CVD. This study was to investigate the association between EP and MetS in the Chinese population. We conducted a retrospective study on 86 consecutive patients with EP and 100 healthy controls from Huashan Hospital between 2013 and 2018. Demographic, biochemical parameters for MetS, and other relevant data including the severity of EP, family history of EP, age of onset, and treatment history involved in those individuals were recorded. The prevalence of MetS in erythrodermic psoriatic patients was 88.37%, which was significantly higher than that of controls (P < 0.0001). Erythrodermic psoriatic patients also had a higher prevalence of MetS components, including abdominal obesity, dyslipidemia and hypertension, whereas hyperglycemia was similar. Adjusted for confounding factors, MetS, abdominal obesity, hypertension, smoking and alcohol use were positive independent predictors of EP (odds ratio > 1, P < 0.05). The area under the receiver operating characteristic curve calculated from determined risk factors for predicting the EP's incidence was 0.934 (95% CI 0.902-0.966). There was no correlation between the severity of EP and the prevalence of MetS. Compared with patients with mild EP, patients with moderate-to-severe EP had higher body mass index, waist circumstance and blood pressure (P < 0.05). We concluded that the prevalence of MetS and its components was higher in patients with EP. MetS an independent predictor of EP, which can favor CVD and should be encouraged to correct these cardiovascular risk factors aggressively for managing EP.

The effects of acupuncture for patients with psoriasis: Study protocol for a randomized controlled trial.

INTRODUCTION: Psoriasis is a common chronic relapsing inflammatory skin disease, which may have considerable detrimental effects on the quality of life. Considering high costs and side effects associated with the use of conventional medications, acupuncture, as one of complementary and alternative nonpharmacological therapies, is commonly used in the management of psoriasis for reducing itching, repairing the skin lesions, etc. However, the effects of acupuncture in the management of psoriasis are still inconsistent, especially in psychosocial abnormality due to psoriasis. Therefore, we designed a randomized controlled trials (RCT) involving a placebo control to ensure participants' blinding to investigate the effects of acupuncture for psoriasis in improving typical clinical symptoms and psychosocial abnormality. METHODS: A singlecenter RCT was designed. 220 participants who meet the eligibility criteria will be randomly allocated into manual acupuncture group or sham acupuncture group in a 1:1 ratio. Participants will respectively receive 15 minutes manual acupuncture or sham acupuncture per session, 3 sessions per week, totally 12 weeks. Psoriasis Area and Severity Index scores, body surface area (BSA), Medical Outcomes Study 36-Item Short-Form Health Survey, Montgomery-Asberg Depression Rating Scale, and Depression, Anxiety, and Stress Scale-21 will be evaluated by blinded operators at baseline and 12 weeks. All analyses will be based on an intention-to-treat principle. The results will be published in an international peer-reviewed journal. DISCUSSION: The results of this study are expected to clarify the effects of acupuncture on improving typical clinical symptoms and psychosocial abnormality of patients with psoriasis. It will contribute to clinical practice of acupuncture in the management of psoriasis. TRIAL REGISTRATION: Chinese Clinical Trail Registry: ChiCTR2100045481. Registration date: April 17, 2021.