Nociceptors as controllers of immunity 3292

Abstract Description Nociceptors – neurons that elicit the sensation of pain or itch in response to noxious stimuli – control immune responses in barrier tissues, however, our understanding of the underlying communication frameworks remains incomplete. To begin to address this gap in our knowledge, we have developed a co-culture system that enables the dissection of neuroimmune interactions between nociceptors and immune cells. In this manner, we found that nociceptors control the functions of dendritic cells (DCs) in three molecularly distinct ways that include direct electrical coupling, the release of the neuropeptide CGRP, and the chemokine CCL2. Accordingly, in the mouse skin, these combined actions of nociceptors, in a context-dependent manner, fine-tune not only DC-dependent local inflammation but also the induction of adaptive immune responses against skin-acquired antigens. Additionally, using a similar approach, we uncovered the ability of nociceptors to induce a myeloid-derived suppressor cell (MDSC) phenotype in monocytes. MDSCs are known to inhibit tumor immunity in various contexts and, indeed, in a mouse model of urinary bladder carcinoma, nociceptor depletion resulted in a decreased tumor burden, which correlated with a lower number of intratumoral MDSCs. Thus, a combination of in vitro and in vivo techniques revealed novel mechanisms of how nociceptors regulate the functions of different myeloid immune cells and control immunity across multiple (patho)physiological conditions. Funding Sources Supported by NIH R01AR068383; NIH R01AI155865; NIH R01AI175379 Topic Categories Neuroimmunology (NEUR)