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Publication : Keratinocyte-Mediated Activation of the Cytokine TGF-β Maintains Skin Recirculating Memory CD8<sup>+</sup> T Cells.

First Author  Hirai T Year  2019
Journal  Immunity Volume  50
Issue  5 Pages  1249-1261.e5
PubMed ID  30952606 Mgi Jnum  J:281014
Mgi Id  MGI:6376388 Doi  10.1016/j.immuni.2019.03.002
Citation  Hirai T, et al. (2019) Keratinocyte-Mediated Activation of the Cytokine TGF-beta Maintains Skin Recirculating Memory CD8(+) T Cells. Immunity 50(5):1249-1261.e5
abstractText  Regulated activation of the cytokine TGF-beta by integrins alphavbeta6 and alphavbeta8 expressed on keratinocytes is required for residence of epidermal-resident memory T cells, but whether skin-derived signals also affect recirculating memory cells in the skin remains unclear. Here, we show that after resolution of skin vaccinia virus (VV) infection, antigen-specific circulating memory CD8(+) T cells migrated into skin. In mice lacking alphavbeta6 and alphavbeta8 integrins (Itgb6(-/-)Itgb8(fl/fl)-K14-cre), the absence of epidermal-activated TGF-beta resulted in a gradual loss of E- or P-selectin-binding central and peripheral memory populations, which were rescued when skin entry was inhibited. Skin recirculating memory cells were required for optimal host defense against skin VV infection. These data demonstrate that skin migration can persist after resolution of local skin infection and that the cytokine environment within this nonlymphoid tissue shapes the differentiation state and persistence of the central and peripheral memory-T-cell pool.
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