Innate cell infiltration into the skin is suppressed in dirty mice following alarming stimulation.

Summary: Abstract Body: Tissue resident memory T (Trm) cells sequestered at barrier tissues are a swift first line defense against peripheral reinfections. Moreover, when aberrantly activated, Trm cells can mediate autoimmune diseases, such as psoriasis. As an effector mechanism Trm cells can stimulate the influx and activation of memory T cells and innate immune cells. However, there is significant heterogeneity in the inflammatory responses that Trm cell populations can induce, specifically in the activation of the innate profile. Most studies to date have utilized a reductionist approach to examine single Trm populations, specific pathogens, and defined tissues. To complement these studies in the skin, we have adopted a holistic approach utilizing barrier-free ‘dirty’ mice to profile activated innate cells attracted into the skin in the presence of quiescent cutaneous Trm cells. Notably, dirty mice are a more human predictive model due to having a diverse microbial experience that leads to the development of a complete complement of Trm cells in the skin. We demonstrate that in the dirty mouse model mice have a significant reduction in cutaneous neutrophils and monocytes compared to specific pathogen free mice following local treatment with two separate innate stimuli. These findings reveal that cutaneous Trm cells have the capacity to temper the innate immune response and further substantiate the implication that Trm cells are heterogenous in their functions depending in large part on their tissue residency. However, in a psoriasiform microenvironment Trm cells are capable of recruiting innate cells to the site of an alarmin exposure. Likely due to the imbalance of IL-17 and IFN-γ. Alicia Mathers^{1, 2}, Meaghan Story¹, Laura K. Ferris³ 1. Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States. 2. Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States. 3. Dermatology, University of North Carolina School of Medicine, Chapel Hill, NC, United States. Adaptive and Auto-Immunity