Credit: Deyan Georgiev-Premium RF/Alamy

The skin is a highly dynamic immune environment that provides a barrier against infection and injury. Two recent studies improve our understanding of skin immune responses; Naik et al. show that dendritic cells (DCs) sense skin commensals and promote distinct CD8+ T cell responses, and Zhang et al. report that dermal adipocytes produce antimicrobial peptides that protect against skin infection.

Whether a new commensal species can become established in the pre-existing skin microbiota and alter immunity at this site has been unclear. Naik et al. found that Staphylococcus epidermidis can colonize the skin of specific pathogen-free mice at multiple sites. This colonization was associated with increased numbers of CD8+ T cells expressing interleukin-17A (IL-17A) and interferon-γ (IFNγ) in the skin, but the response was not associated with inflammation. The authors found that colonization of mouse skin with six out of eight different human- or mouse-specific commensals led to an increase in the numbers of skin IL-17A+ T cells and/or IFNγ-producing T cells. Hence, when the skin encounters certain new commensals, it can lead to a robust non-inflammatory accumulation of CD8+ T cells with a distinct cytokine profile.

skin-resident DCs seem to cooperate in responding to changes in the commensal community

Next, Naik et al. investigated whether DCs have a role in sensing changes in the skin microbiota. Indeed, the CD8+ T cell response to S. epidermidis was abolished in mice lacking CC-chemokine receptor 7, which regulates the migration of DCs. Although the frequency of skin DC subsets was unaltered upon commensal colonization, the authors examined the relative contribution of CD103+ DCs (which depend on IFN-regulatory factor 8 (IRF8) and basic leucine zipper transcription factor ATF-like 3 (BATF3) to develop) and CD11b+ DCs (which require colony-stimulating factor 1 (CSF1)) to the CD8+ T cell response. Mice lacking IRF8 and BATF3 failed to mount CD8+ T cell responses following colonization with S. epidermidis,and treating mice with an antibody specific for the CSF1 receptor led to decreased numbers of CD11b+ DCs and skin IL-17A+ CD8+ T cells. Similarly to what has previously been seen in the gut, colonization of the skin with commensals seems to induce the development of CD4+ T helper 17 cells, whereas the induction of CD8+ T cells seems to be unique to the skin. Finally, exposure of skin CD8+ T cells to S. epidermidis-loaded DCs lacking β2-microglobulin-dependent MHC class I presentation did not induce increased production of IL-17A. Thus, skin-resident DC subsets seem to cooperate in responding to changes in the commensal community to induce CD8+ T cell responses that promote the production of antimicrobial peptides by keratinocytes and thereby protect against subsequent infections.

The study by Zhang et al. showed that the number and size of local subcutaneous adipocytes increased in response to Staphylococcus aureus skin infection, and that mice with impaired adipogenesis had increased susceptibility to S. aureus skin infection. When comparing the expression of antimicrobial peptides during adipogenesis, the authors found that the production of cathelicidin antimicrobial peptide (CAMP) by either mouse or human cells greatly increased when preadipocytes were stimulated to become differentiated adipocytes. Furthermore, cathelicidin protein and mRNA were strongly induced in adipocytes at the site of infection, and their expression was decreased when adipogenesis was inhibited. Finally, adipocytes from Camp-deficient mice did not exhibit antimicrobial properties. Thus, the local expansion of adipocyte populations is an important skin immune response to infection.

Together, these studies increase our understanding of skin immunity by showing that a previously unrecognized interaction between skin DCs and commensals drives CD8+IL-17A+T cell development in the skin and by identifying a novel role for adipocytes in promoting the production of antimicrobial peptides.