Regulation and function of CCR2 on T cells in Rheumatoid Arthritis

NIH RePORTER · NIH · F31 · $36,856 · view on reporter.nih.gov ↗

Abstract

Abstract Rheumatoid Arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of the synovium and infiltration of mononuclear cells into the joint. Once in the joint the mononuclear cells, predominantly T cells and macrophages, contribute significantly to disease pathology, yet the mechanism by which these cells enter the joint is not clearly established. To answer this question, we decided to investigate the expression of chemokine receptors on infiltrating T cells. Chemokine receptors are transmembrane protein receptors that facilitate immune cell migration towards gradients of their respective cytokines. Previous work in the lab found a large population of T cells in the inflamed synovium express the chemokine receptor CCR2. In addition, work from other groups have consistently shown an elevated expression of CCR2 in RA patient blood, however, there have not been investigations into T cell specific loss of CCR2 in RA. Additionally, chemokine receptors are often used as markers to identify functional subsets of helper T cells. Considering the robust population of T cells expressing CCR2 in the inflamed synovium, we hypothesized that CCR2 may facilitate migration or positioning within the inflamed synovium and may demarcate a functional T cell population. Furthermore, very little is known about the regulation of CCR2 expression on T cells and better understanding of its regulation could allow for modulation of the proposed migratory or functional programming. Therefore, we are proposing a robust investigation into the regulation and function of CCR2 in T cells utilizing cytometric, transcriptomic, functional, and murine systems to thoroughly characterize this population and better understand its role in RA pathogenesis.

Key facts

NIH application ID
10810661
Project number
5F31AR082658-02
Recipient
HARVARD MEDICAL SCHOOL
Principal Investigator
Sabrina Esmeralda Bracero
Activity code
F31
Funding institute
NIH
Fiscal year
2024
Award amount
$36,856
Award type
5
Project period
2023-05-01 → 2026-04-30