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- W4366186923 abstract "CD4+ tissue-resident memory T (TRM) cells persist in the skin after an allergic reaction and induce rapid inflammation upon antigen re-exposure. However, the mechanisms underlying the maintenance of CD4+ TRM cells and their functional heterogeneity remain largely unknown. To clarify this, we first used a delayed-type hypersensitivity model with adaptive transfer of ovalbumin (OVA)-specific CD4+ T cells using T cell receptor-β deficient mice as recipients. Mice were sensitized with OVA emulsion and then challenged with OVA in the ear skin (day 0). On day 35, when the ear swelling had resolved, CD4+ T cells remained in the dermis with a CD44+CD69+ TRM cell phenotype. Consistently, parabiosis experiments confirmed their tissue residency. Immunohistochemical analysis revealed that CD4+ TRM cells formed clusters with CD301b+ dermal dendritic cells. To address the importance of its interaction, we selectively depleted CD301b+ cells using CD301b-diphtheria toxin receptor mice, and found that the number of CD4+ TRM cells and their clusters decreased after the depletion. In addition, the depletion of CD301b+ cells reduced the transcription level of CXC-chemokine ligand 16 (CXCL16). And its receptor, CXC-chemokine receptor 6 (CXCR6), was preferentially expressed on CD4+ TRM cells. We found that blocking CXCL16 inhibited the proliferation of CXCR6+CD4+ TRM cells and attenuated the rapid ear swelling upon re-challenge. Finally, RNA-sequencing revealed that CXCR6+CD4+ TRM cells produced IFN-γ and IL-13 upon re-challenge, whereas CXCR6-CD4+ TRM cells displayed Foxp3+ regulatory T cell phenotype. Taken together, these results indicate that CXCR6+CD4+ TRM cells play a pathogenic role during the recall responses by producing effector cytokines, and its maintenance is mediated by interacting with CD301b+ dendritic cells via CXCL16. This mechanism provides a new strategy for preventing the recurrence of chronic allergic skin diseases, such as atopic dermatitis." @default.
- W4366186923 created "2023-04-19" @default.
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- W4366186923 date "2023-05-01" @default.
- W4366186923 modified "2023-09-28" @default.
- W4366186923 title "074 Newly identification of a CXCR6+ pathogenic skin-resident CD4+ T cell subset in a mouse model of allergic dermatitis that requires CXCL16 for its maintenance" @default.
- W4366186923 doi "https://doi.org/10.1016/j.jid.2023.03.075" @default.
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