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CD109 Restrains Activation of Cutaneous IL-17-Producing γδ T Cells by Commensal Microbiota

2019; Cell Press; Volume: 29; Issue: 2 Linguagem: Inglês

10.1016/j.celrep.2019.09.003

2639-1856

Hualin Zhang, Giustino Carnevale, Barbara Polese, Mélissa Simard, Bavanitha Thurairajah, Nargis Khan, Maria E. Gentile, Ghislaine Fontès, Donald C. Vinh, Roxane Pouliot, Irah L. King,

Immune Cell Function and Interaction

Interleukin-17-producing γδ T (γδ17) cells play a central role in protective and pathogenic immune responses. However, the tissue-specific mechanisms that control the activation of these innate lymphocytes are not known. Here, we demonstrate that CD109, a glycosylphosphatidylinositol (GPI)-anchored protein highly expressed by keratinocytes, is an important regulator of skin homeostasis and γδ17 cell activation. Genetic deletion of CD109 results in spontaneous epidermal hyperplasia, aberrant accumulation of dermal-derived γδ17 cells, and enhanced susceptibility to psoriasiform inflammation. In this context, γδ17 activation requires interleukin (IL)-23 signals and is reversed by transient depletion of the skin microbiota. Mechanistically, CD109 restrains γδ17 cell activation in a cell-extrinsic manner by fortifying skin barrier integrity. Collectively, our data provide insight into the regulation of the skin IL-23/IL-17 immune axis and how homeostasis is maintained at this important barrier site.