Project Details
Projekt
Crosstalk between Foxp3+ Regulatory T Cells and Type 2 Immunity in Maintaining Adipose Tissue Homeostasis
Subject Area
Immunology
Term
from 2017 to 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 322359157
Emerging evidence is pointing towards a major role of type 2 immunity in maintaining metabolic homeostasis of the lean adipose tissue (AT). In this context, type 2 immune cells such as M2-macrophages, type 2 innate lymphoid cells and eosinophils, as well as cardinal cytokines of type 2 immunity (IL-4, IL-13) appear of particular relevance. Consistently, the manifestation of obesity is accompanied by a switch towards type 1 immunity with enhanced accumulation of M1-polarized macrophages, pathogenic CD4+ and CD8+ T effector cells, and proinflammatory cytokines (TNF, IL-6) that promote insulin resistance of the AT. Notably, a unique subphenotype of CD4+ regulatory T (Treg) cells co-expressing Foxp3 and PPAR- has been shown to be enriched in the lean AT and to critically contribute to the maintenance of AT homeostasis, although the underlying mechanisms have yet to be identified. Conversely, the population size of such AT-residing Treg cells markedly decreases in obesity. Overall, independent lines of evidence have firmly established that AT-residing type 2 immune and Foxp3+ Treg cells resent important players in the control of AT metabolism, while the exact molecular and cellular mechanisms involved have remained ill-defined. In particular, it has remained unclear to what extent type 2 immune cells (e.g. eosinophils) and Treg cells cooperate in maintaining AT homeostasis, and whether naturally induced Foxp3+ Treg cells of thymic and peripheral origin exert specialized functions in this process. These important questions will be addressed in the present proposal.
DFG Programme
Research Units
