RAMP3 unexplored relevance for innate-T cell immunity

Abstract RAMP3 is a chaperon protein that aids in the transport, activity modulation and pharmacological switch of G-protein coupled receptors (GPCR). Chemokine receptors involved in immune cell recruitment and activation are GPCRs, but the role of RAMP3 in the function of the immune system has not been explored. Our lab found that Ramp3 gene is highly expressed in innate-like T cells in the lungs of mice, particularly for Mucosal-associated invariant T (MAIT) cells. Ramp3 KO mice have an increased absolute number of MAIT cells, while other innate T cells are not affected. These differences are even higher after vaccinations with a live attenuated Salmonella strain containing MAIT-cell antigens. Both at steady-state and after vaccination, Ramp3 KO mice MAIT cells have increased levels of CXCR6, a chemokine receptor that has been associated to lung homing and T cell maintenance in the periphery. Ramp3 KO mice also have a decreased proportion of IL17A-producing MAIT cells in the lung; IL-17-producing innate cells have been shown to be protective, for example following Streptococcus pneumoniae infection. Consistent with the MAIT17 decrease, there was increased bacterial burden after lung infections. While Ramp3 has been reported in several gene signatures related to T cell regulation, its role for T cell immunity has not been explored. This is the first evidence of the relevance of Ramp3 for immune cell function and host protection, influencing innate-like T cell mediated immune function and protection against lung bacterial infections. Supported by grants from NIH 5R01AI137230-04