TY - JOUR AU - Lei, Yuk Man AU - Sepulveda, Martin AU - Chen, Luqiu AU - Wang, Ying AU - Pirozzolo, Isabella AU - Theriault, Betty AU - Chong, Anita S. AU - Belkaid, Yasmine AU - Alegre, Maria-Luisa T1 - Skin-restricted commensal colonization accelerates skin graft rejection PY - 2019/08/08/ AB - Solid organ transplantation can treat end-stage organ failure, but the half-life of transplanted organs colonized with commensals is much shorter than that of sterile organs. Whether organ colonization plays a role in this shorter half-life is not known. We have previously shown that an intact whole-body microbiota can accelerate the kinetics of solid organ allograft rejection in untreated colonized mice, when compared with germ-free (GF) or with antibiotic-pretreated colonized mice, by enhancing the capacity of antigen-presenting cells (APCs) to activate graft-reactive T cells. However, the contribution of intestinal versus skin microbiota to these effects was unknown. Here, we demonstrate that colonizing the skin of GF mice with a single commensal, Staphylococcus epidermidis, while preventing intestinal colonization with oral vancomycin, was sufficient to accelerate skin graft rejection. Notably, unlike the mechanism by which whole-body microbiota accelerates skin graft rejection, cutaneous S. epidermidis did not enhance the priming of alloreactive T cells in the skin-draining lymph nodes. Rather, cutaneous S. epidermidis augmented the ability of skin APCs to drive the differentiation of alloreactive T cells. This study reveals that the extraintestinal donor microbiota can affect transplant outcome and may contribute to the shorter half-life of colonized organs. JF - JCI Insight JA - JCI Insight SN - 2379-3708 DO - 10.1172/jci.insight.127569 VL - 4 IS - 15 UR - https://doi.org/10.1172/jci.insight.127569 PB - The American Society for Clinical Investigation ER -