Accession Number : AD1047486


Title :   The Role of the Interferon-Gamma-Jak/STAT Pathway in Rheumatoid Arthritis


Descriptive Note : Technical Report,01 Sep 2016,31 Aug 2017


Corporate Author : University of Alabama at Birmingham Birmingham United States


Personal Author(s) : Bridges, Stanley Jr L


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1047486.pdf


Report Date : 01 Sep 2017


Pagination or Media Count : 18


Abstract : Type I (IFN-) and type II (IFN-) interferons are important mediators of autoimmunity. Our group recently showed a strong association of IFN- receptor 1 (Ifngr1) expression and of IFN- receptor 2 (Ifngr2) expression in peripheral blood mononuclear cells (PBMC) with the presence of RA and its radiographic severity, respectively (Arthritis Rheumatol. 2015 67:1165). IL-2 has essential regulatory function in inflammatory diseases and is considered as a potential therapy for autoimmune disease. We tested the hypothesis that RA is associated with alterations in IFN- and IL-2 STAT signaling within certain subsets of PBMCs. We used a high-definition phospho-flow approach to evaluate the activation of STAT1, STAT3 and STAT5 after IFN- or IL-2stimulation. We analyzed PBMCs from 37 RA patients and 12 healthy controls (HC) for activation of STATs in specific CD4and CD8 T cells subpopulations, B cells and monocytes. We found that IFN- induced STAT1 activation was significantly greater in RA nave, central memory, Tfh and Treg subsets of CD4 T cell populations compared to HC (p0.05). IL-2 very efficiently activated STAT5 in all T and B cell populations in RA and HC. The activation of STAT5 in RA was significantly greater than HC in only one population: effector memory CD4 T cells (p0.01). Our studies revealed the presence of a STAT5phosphatase in RA T cell subsets that likely counteracts IL-2 regulator activity and contribute to the pathogenesis of RA.


Descriptors :   ARTHRITIS , joint diseases , Autoimmunity , interferon , therapeutics


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE