The role of NLRP1 inflamassome in the antitumor response of Th17 limphocytes

Abstract

Cellular metabolism has become central to the balance of the immune response. Several evidences show that one of the main factors to govern the balance between Th17 and Treg lymphocytes is lipid metabolism. NLRP1 is an inflammasome complex, capable of activating caspase-1 and is highly expressed in the skin. Differences exist between their murine and human models. Accumulated evidence shows a possible relationship between NLRP1 and metabolism. NLRP1 - / - mice develop spontaneous obesity, mediated by fatty accumulation and decreased lipolysis rates. In addition, several activities related to NLRP1 can be inserted in the metabolic context of fatty oxidation (FAO). In turn, a relationship between NLRP1 and a generation of Th17 lymphocytes is observed in inflammatory conditions, such as diabetes or NLRP1 - / - mice shows an increase in Th17 lymphocytes. This project has the hypothesis that NLRP1 promotes oxidative phosphorylation, and this can cause the inhibition of the activation of lymphocytes with a Th17 profile, in environments such as the tumor microenvironment. Mice (NLRP1 - / - and WT) will be used and the metabolic profile, expression of classic markers, and expression and activation of NLRP1 will be verified in the Th17 and Treg statistics by Seahorse technology, qRT-PCR, flow cytometry, Western Blot and quantification of IL-1b respectively. FAO will be analyzed in a similar way from its blockage by etomoxir. Finally, the subtypes Th1, Th17 and Treg will be quantified in the murine melanoma models. (AU)