AB0258 Decreased Phosphostat5 Contributed To Impairment of CD4+CD25+Foxp3+ Tregs in RA Patients

Abstract

BackgroundOur previous research has demonstrated decreased expression of CD4+CD25+Foxp3+ regulatory T cells (Tregs) enrolled in the pathogenesis of rheumatoid arthritis (RA). Anti-TNF-α mAb therapy could improve Tregs expansion in RA and associate with clinical amelioration of RA patients. STAT5 is reported to have effects on many aspects of immune function, particularly in regulatory T cell development.ObjectivesIn this study, we aim to monitor phosphoSTAT5 expression in Tregs and investigate its role in RA disease.MethodsFlowcytometry was employed to detect the phosphorylation level of STAT5 in CD3+CD4+ T cells, CD4+CD25high regulatory T cells and the expression of CD4+CD25+Foxp3+Tregs in peripheral blood of 20 patients with RA disease and 20 age and gender-matched normal controls. STAT5 mRNA expression in peripheral blood mononuclear cells (PBMC) were also monitored of these RA patients and normal controls.ResultsPhosphorylation level of STAT5 deceased in RA patients both in CD3+CD4+ T cells and in CD4+CD25high regulatory T cells, along with reduction of expression of CD4+CD25+Foxp3+ Tregs. Detection of mRNA also confirmed STAT5 down regulation in Tregs in RA patients.ConclusionsCompared with normal controls, the expression of CD4+CD25+Foxp3+Tregs decreased in RA patients. PhosphoSTAT5 reduction in CD3+CD4+ T cells, mainly in CD4+CD25high regulatory T cells contributed to impairment of CD4+CD25+Foxp3+ regulatory T cells in RA.ReferencesNiu Q, Cai B, Huang ZC, Shi YY, Wang LL. Disturbed Th17/Treg balance in patients with rheumatoid arthritis. Rheumatol Int. 2012 Sep;32(9):2731–6.Huang Z, Yang B, Shi Y, Cai B, Li Y, Feng W, Fu Y, Luo L, Wang L. Anti-TNF-α therapy improves Treg and suppresses Teff in patients with rheumatoid arthritis. Cell Immunol. 2012 Sep;279(1):25–9.Disclosure of InterestNone declared

Anti-CCL22 increases regulatory T�cells in CD4+ T�cells of rheumatoid arthritis patients via STAT5 pathway

“…Tregs with the high levels of p-STAT5 is frequently associated with the high suppressive activity in vitro (17). Expression levels of p-STAT5 is down regulated in Tregs in RA patients (17). In this study, we suggest that the activation of STAT5 was accelerated by anti-CCL22 antibody (Fig.…”

“…Activation of STAT5 is sufficient to increase the number of Tregs and favors Tregs homeostasis and self-tolerance (16). Tregs with the high levels of p-STAT5 is frequently associated with the high suppressive activity in vitro (17). Expression levels of p-STAT5 is down regulated in Tregs in RA patients (17).…”

Increased Serum Interleukin-2 Levels Are Associated with Abnormal Peripheral Blood Natural Killer Cell Levels in Patients with Active Rheumatoid Arthritis

“…Treg cells protect against arthritis in collagen-induced arthritis mouse models, in which depletion of Treg cells leads to exacerbation of arthritis; supplementation of exogenous Treg cells not only delays progression of the disease [ 20 ] but also inhibits generation of osteoclasts and promotes increased bone mass [ 21 ]. Many studies have shown that, compared with healthy individuals, the percentage of circulating Treg cells is reduced in RA patients [ 22 ], implying that the decrease in Treg cells is closely related to the disease progression of RA. Th17 cells, as proinflammatory cells, mediate pannus growth, osteoclast formation, and synovial neovascularization and are a key player in disease development [ 23 ].…”