Neutrophil recruitment by CD4 tissue-resident memory T cells induces chronic recurrent inflammation in atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease that continues to impose significant physical, mental, and economic burdens on patients. Recent research has suggested the significant role of tissue-resident memory (TRM) cells in AD. However, the precise role and mechanisms of action of TRM cells in AD remain unclear. A deeper understanding of the involvement of TRM cells in AD will unveil promising pathways for future innovative therapeutic strategies. METHODS: To investigate the involvement of TRM cells in AD, we used diverse mouse models and employed experimental techniques to manipulate cell formation and depletion. We assessed the inflammatory response by analyzing mouse ear phenotype, measuring ear thickness, and performing hematoxylin and eosin staining. Flow cytometry and immunofluorescence staining were used to identify different cell types and evaluate changes in cell quantity. Additionally, we used qPCR to analyze gene expression of relevant chemokines and cytokines. RESULTS: Our study revealed the presence of TRM cells in the skin after exposure to calcipotriol. After a 24-h re-challenge, we observed substantial neutrophil infiltration into the previously irritated skin. Neutrophil depletion prior to re-challenge effectively prevented early flare-up responses during AD recurrence. Furthermore, we demonstrate that CD4+TRM cells upregulate expression of cytokines INF-γ and TNF-α, which may induce the expression of CXCL1, thereby recruiting neutrophils and contributing to the chronic recurrent inflammation observed in AD. CONCLUSIONS: We have established a novel, chronic recurrent mouse model for investigating TRM cells in AD. Our findings demonstrate that CD4+TRM cells in the skin mediate early flare-up response during AD recurrence and influence the chronic recurrent inflammation of AD by recruiting neutrophils. Targeting CD4+TRM cells may represent a promising approach for the treatment of chronic recurrent inflammation in AD.

Allergen Sensitization in Patients with Skin Diseases in Shanghai, China.

Introduction: Allergen distribution has obvious geographical characteristics. Understanding local epidemiological data may provide evidence-based strategies for the prevention and management of disease. We investigated the distribution of allergen sensitization in patients with skin diseases in Shanghai, China. Methods: Data from tests for serum-specific immunoglobulin E were collected from 714 patients with three skin diseases who visited the Shanghai Skin Disease Hospital from January 2020 to February 2022. The prevalence of 16 allergen species, as well as age, sex, and disease-group differences in allergen sensitization, were investigated. Results: Dermatophagoides farinae and Dermatophagoides pteronyssinus were the most common aeroallergen species to cause allergic sensitization in patients with skin diseases, whereas shrimp and crab were the most common food-allergen species. Children were more susceptible to various allergen species. With regard to sex differences, males were sensitized to more allergen species than females. Patients suffering from atopic dermatitis were sensitized to more allergenic species than patients with non-atopic eczema or urticaria. Conclusion: Allergen sensitization in patients with skin diseases in Shanghai differed by age, sex, and disease type. Knowing the prevalence of allergen sensitization across age, sex, and disease type may help facilitate diagnostic and intervention efforts, and guide the treatment and management of skin diseases in Shanghai.

T cell co-stimulatory and co-inhibitory pathways in atopic dermatitis.

The use of immune checkpoint inhibitors (ICIs) targeting the T cell inhibitory pathways has revolutionized cancer treatment. However, ICIs might induce progressive atopic dermatitis (AD) by affecting T cell reactivation. The critical role of T cells in AD pathogenesis is widely known. T cell co-signaling pathways regulate T cell activation, where co-signaling molecules are essential for determining the magnitude of the T cell response to antigens. Given the increasing use of ICIs in cancer treatment, a timely overview of the role of T cell co-signaling molecules in AD is required. In this review, we emphasize the importance of these molecules involved in AD pathogenesis. We also discuss the potential of targeting T cell co-signaling pathways to treat AD and present the unresolved issues and existing limitations. A better understanding of the T cell co-signaling pathways would aid investigation of the mechanism, prognosis evaluation, and treatment of AD.

[The Molecular Mechanism of LncRNA-CASC2/miR-155-5p/APC Axis Regulating the Progression of Non-Hodgkin Lymphoma].

OBJECTIVE: To investigate the effect of lncRNA-CASC2 (CASC2) /miR-155-5p/APC axis to the progression of non-Hodgikn lymphoma (NHL). METHODS: The expression level of CASC2 and miR-155-5p in NHL cell lines were examined by qRT-PCR. Dual-luciferase reporter gene assay was used to verify the relationship between miR-155-5p, CASC2 and APC. The effects of CASC/miR-155-5p/APC axis to the proliferation, invasion and apoptosis of NK-92 cells were detected by MTT, Transwell assay and flow cytometry assay, respectively. RESULTS: CASC2 was downregulated in NHL cell lines. Overexpression of CASC2 could inhibit the proliferation and invasion of NK-92 cells, and promote its apoptosis. Dual-luciferase reporter gene assay confirmed that there was a targeting relationship between miR-155-5p, CASC2 and APC. The restoration experiments proved that knockdown of both miR-155-5p and CASC2 or APC could restore the inhibitory effect of miR-155-5p silencing to the biological behavior of NK-92 cells. CONCLUSION: Overexpression of CASC2 suppresses the proliferation and invasion of NK-92 cells, promote the apoptosis of NK-92 cells via targeting miR-155-5p and upregulating APC expression.