Keratinocyte-Mediated Activation of the Cytokine TGF-β Maintains Skin Recirculating Memory CD8+ T Cells

Toshiro Hirai, Yukari Zenke, Yi Yang, Laurent Bartholin, Lalit K. Beura, David Masopust, Daniel H. Kaplan

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Regulated activation of the cytokine TGF-β by integrins αvβ6 and αvβ8 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 αvβ6 and αvβ8 integrins (Itgb6−/−Itgb8fl/fl-K14-cre), the absence of epidermal-activated TGF-β 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.

Original languageEnglish (US)
Pages (from-to)1249-1261.e5
JournalImmunity
Volume50
Issue number5
DOIs
StatePublished - May 21 2019

Bibliographical note

Funding Information:
We thank the members of the Kaplan laboratory and Vignali laboratory and members throughout the departments of Dermatology and Immunology for helpful discussions. We also thank the Division of Laboratory Animal Resources of the University of Pittsburgh for excellent animal care. This work benefitted from a SPECIAL BD LSRFortessa funded by NIH 1S10OD011925-01. T.H. was supported by JSPS Overseas Research Fellowships and D.H.K. by NIH R01AR060744. T.H. and D.H.K. designed and interpreted experiments; T.H. Y.Z. and Y.Y. performed experiments; L.K.B. and D.M. provided technical and conceptual assistance; L.B. contributed a critical reagent. T.H. and D.H.K. wrote the manuscript, and all authors edited it. The authors declare no competing interests.

Funding Information:
We thank the members of the Kaplan laboratory and Vignali laboratory and members throughout the departments of Dermatology and Immunology for helpful discussions. We also thank the Division of Laboratory Animal Resources of the University of Pittsburgh for excellent animal care. This work benefitted from a SPECIAL BD LSRFortessa funded by NIH 1S10OD011925-01 . T.H. was supported by JSPS Overseas Research Fellowships and D.H.K. by NIH R01AR060744 .

Publisher Copyright:
© 2019 Elsevier Inc.

Keywords

  • CD8 T cell memory
  • keratinocytes
  • skin
  • transforming growth factor beta
  • αβ
  • αβ

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