The skin functions as the primary barrier between an organism and the outside world. Although it is home to a robust and diverse community of commensal microorganisms, it must also prevent entry of environmental toxins, irritants, and numerous viral, bacterial and parasitic pathogens. To effectively maintain its barrier function, the skin must undergo rapid and highly efficient tissue repair when damaged or compromised, and this is associated with local antimicrobial and inflammatory responses that help prevent or combat concurrent infection. Consistent with its functions in maintaining barrier integrity and preventing infection, the skin is home to a number of specialized T cell populations. Using 33-parameter CyTOF (Cytometry by time-of-flight) analysis and standard flow cytometry we have identified a novel population of CLA+CD4+ T cells in the peripheral blood of healthy subjects that expresses the CD103 integrin and produces the novel cytokine combination of IL-22, GM-CSF and IL-13 upon activation (CD103+CLAhi cells). Interestingly, this cytokine combination is also produced by epidermal CD103+CLAhiCD69+ TRM in the skin itself. Based on the ability of IL-22 to promote keratinocyte proliferation, migration and production of antimicrobial peptides, and GM-CSF and IL-13 to act on fibroblasts, and to mediate the differentiation of monocytes and macrophages into 'alternatively activated' cells that promote tissue repair, we are currently testing the impact of CD103+CLAhi cells on skin repair functions. In summary, we have identified a circulating population that resembles skin TRM and might be useful in studying (recirculating?) skin TRM.