Accession Number:

AD1116522

Title:

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

Descriptive Note:

Technical Report,01 Sep 2016,31 Aug 2020

Corporate Author:

University of Alabama at Birmingham Birmingham United States

Personal Author(s):

Report Date:

2020-12-01

Pagination or Media Count:

24.0

Abstract:

This project addresses the hypothesis that elevated andor altered IFN- signaling within selective subsets of mononuclear cells promotes disease severity in RA. This study developed from our novel observation that in peripheral blood the expression levels of interferon gamma receptor 1 IFNGR1 is associated with RA and the expression levels of IFNGR2 correlates significantly with the degree of radiographic damage in RA patients. The aims of this proposal are 1 To identify the specific circulating cell type in which IFNGR expression is elevated in RA. Using a combination of molecular biological and immunological approaches, we will analyze the expression levels of IFNGR1 and IFNGR2 in monocytes, nave and memory B cell populations, nave and memory T cell populations including T-follicular helper cells, Treg cells and T helper effector subpopulations Th1, Th17 and Th171. 2 To determine the outcome of IFNGR signals by assaying the activation of IFN- induced STAT1 and changes in activation of STAT3 and STAT5 in RA versus healthy controls, at basal level and following stimulation with cytokines such as IL-2, IL6 etc. 3 To determine the molecular mechanism and outcome of attenuated IL-2 induced activation of STAT5 in specific subpopulations of T cells in RA. The information to be gained can potentially help to identify new cell signaling targets, perhaps cell-type specific, for RA and other autoimmune diseases, and perhaps malignancies. This in turn may help to develop new drugs that are more targeted, either to particular cell types or patients in whom these cell types are most important to the disease. Ultimately, this may lead to more effective, and safer drugs with fewer adverse effects.

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE