Role of Sex Differences in the Expression & Function of Regulatory T cells in SLE

University Of California Los Angeles, Los Angeles CA

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Abstract

DESCRIPTION (provided by applicant): Regulatory CD4+T cells and CD8+T cells have important roles in suppressing autoimmune disease in the peripheral immune system. Impaired function of regulatory/suppressor T cells contributes to development of autoimmunity. The goal of this project will be studying the quantities and functions of T regulatory cells in healthy controls and patients with SLE, comparing males to females in both groups (given the fact that lupus disease is much more frequent in females than in males). The first aim is to quantify, immunophenotype, and perform functional analysis of the Treg cell subsets in healthy controls, and in male lupus vs female lupus. The second aim is to compare gene expression profiles of CD4+CD25+hiTreg and CD8+Ts cells in male vs female lupus patients and to compare them with healthy controls. Finally, we will test the effect of testosterone and estradiol in these cells in vitro to see their effects on cell phenotypes, gene expression, signaling and regulatory functions. The overall purpose is to understand the molecular network of these CD4+T regulatory cells and CD8+ suppressor cells in systemic autoimmunity. PUBLIC HEALTH RELEVANCE: We propose to study regulatory T cells (CD4 and CD8) (comparing male to female SLE patients and male to female healthy individuals) for quantities, suppressive capacities and differences in gene expression. The ability of sex hormones to change Treg numbers, functions, and gene expression will be studied.