The role of Blimp-1 in adipose Treg differentiation and effector function

Abstract Visceral adipose tissue regulatory T cells (VAT Tregs) protect against systemic inflammation and metabolic disease by limiting expansion of pro-inflammatory Th1 cells and M1 macrophages, and by preserving insulin sensitivity and glucose tolerance. Although their basic markers and roles have been studied, less is known about the transcriptional machinery regulating their differentiation and function. B lymphocyte-induced maturation protein-1 (BLIMP-1) is a transcriptional regulator known to be involved in the development, polarization, and maintenance of various immune cells including CD4+ T cells. Using BLIMP-1 reporter mice, we have discovered that BLIMP-1 is constitutively expressed in a subset of VAT Tregs compared to lymphoid Tregs, and that BLIMP-1+ VAT Tregs are phenotypically distinct from their BLIMP-1-counterparts. Blimp-1 is not required for VAT Treg development, however Treg-specific deletion of BLIMP-1 led to unique changes in VAT Treg markers in lean versus obese adipose tissue. Based on these preliminary data, our project aims to elucidate the role of BLIMP-1 in shaping the VAT Treg compartment and to explore a possible role for BLIMP-1+ VAT Tregs in metabolic co-morbidities such as obesity and Type II diabetes.