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 i s 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 i s 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.
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.
| Singh, Ram Pyare; Hasan, Sascha; Sharma, Sherven et al. (2014) Th17 cells in inflammation and autoimmunity. Autoimmun Rev 13:1174-81 |
| Sawla, Priya; Hossain, Awlad; Hahn, Bevra H et al. (2012) Regulatory T cells in systemic lupus erythematosus (SLE); role of peptide tolerance. Autoimmun Rev 11:611-4 |
| Singh, Ram P; Waldron, Richard T; Hahn, Bevra H (2012) Genes, tolerance and systemic autoimmunity. Autoimmun Rev 11:664-9 |
| Dinesh, R; Hahn, B H; La Cava, A et al. (2011) Interferon-inducible gene 202b controls CD8(+) T cell-mediated suppression in anti-DNA Ig peptide-treated (NZB × NZW) F1 lupus mice. Genes Immun 12:360-9 |
| Dinesh, Ravi K; Hahn, Bevra H; Singh, Ram Pyare (2010) PD-1, gender, and autoimmunity. Autoimmun Rev 9:583-7 |
| Dinesh, Ravi K; Skaggs, Brian J; La Cava, Antonio et al. (2010) CD8+ Tregs in lupus, autoimmunity, and beyond. Autoimmun Rev 9:560-8 |
| Singh, R P; Dinesh, R; Elashoff, D et al. (2010) Distinct gene signature revealed in white blood cells, CD4(+) and CD8(+) T cells in (NZBx NZW) F1 lupus mice after tolerization with anti-DNA Ig peptide. Genes Immun 11:294-309 |
