Age-dependent signals driving dendritic cells to promote type II immunity
Barbara Schraml-Schotta, Biomedical Center, Walter-Brendel-Centre of Experimental Medicine, LMU Munich
Allergic diseases often develop in early life and the incidence of childhood allergies continues to rise. cDCs are key activators of T cells that critically determine the outcome of allergen encounter. In early life, cDCs exhibit qualitative differences compared to adult life, including an intrinsic bias to stimulate type II immunity, which promotes allergic responses by inducing a bias towards Th2 effector and memory responses. However, the signals that regulate cDC function with age remain poorly defined. Microbiome-derived signals and metabolites act as important rheostats for immunoregulation and altering microbial encounter in early life can have lasting influence on the development of allergic diseases. Commensally-derived signals can impact cDC function, but how neonatal commensal encounter influences cDC2, the main cDC subtype to promote type II immunity, has not been investigated. We investigate how perturbing the neonatal microbial encounter affects cDC2 transcriptional profiles and function in early and adult life. Our goal is to generate a transcriptional atlas of gene expression in cDC2 with age allowing us to determine how cDC2 subset composition and transcriptional profiles change with age and in different organs. These experiments will shed light on the mechanisms, by which commensal microbes influence susceptibility to allergic disease in adulthood. Because preliminary data indicate that age dependent cytokine environments, possibly in response to commensal microbes, imprint cDC2 function, we will use mice with genetic deficiency in cytokine signalling and cDC lineage specific knock out mice to gain mechanistic insights into the regulation of DC2 function with age.
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