Résumé
Infectious agents are estimated to cause approximately 18% of cancers worldwide, supporting a link between microbial products and carcinogenesis. The microbiome consists of a diverse array of commensal microorganisms that reside at barrier sites of the human body and promote local immune homeostasis, but also provide the primary source of constitutive microbial stimulation. While recent work has demonstrated that intestinal commensals can influence immunity throughout the body, the distal effects of other microbial communities have not been fully explored. Here we show that application of distinct human commensals to the skin of mice induces the accumulation of IL-17A-producing T cells in the lungs. The induction of these cells occurs in a manner that is partially dependent on both antigen presentation and IL-23 signaling. Response kinetics and adoptive transfer experiments suggest that the T cells migrate from the skin-draining lymph nodes, while transcriptional analysis has identified specific chemokine receptors that facilitate trafficking to the lungs. Furthermore, in the context of a pulmonary challenge, cutaneous application of commensals promotes the production of IL-17A and recruitment of neutrophils to the lungs. This work demonstrates that the skin microbiome can enhance pulmonary immunity, but also has the potential to cause pro-oncogenic inflammation. Since IL-17A promotes tumor vascularization and neutrophils can contribute to the establishment of metastases, specific microbes at distal sites such as the skin may exacerbate the progression of lung cancer. Citation Format: Michael G. Constantinides, Vanessa K. Ridaura, Yasmine Belkaid. Cutaneous microbiota drive the accumulation of IL-17A-producing T cells within the lungs [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A076.