Good news!
"Nearly 1.5 million Americans and nearly 5% of women over the age of 55 have rheumatoid arthritis (RA), an incurable autoimmune disease marked by joint inflammation and subsequent damage. ...
T lymphocytes ... the study found that some of these lymphocytes have a receptor for the immune hormone macrophage migration inhibitory factor, or MIF, on their surface.
Previous research has shown that many individuals with autoimmunity have overactive forms of the MIF gene ...
The researchers discovered that these T lymphocytes are expanded in mouse models of joint inflammation and that simply transferring these particular cells to healthy mice caused RA-like joint inflammation. The research team went on to identify these novel MIF-sensitive T lymphocytes in joint tissue from patients with RA who needed joint replacement.
“These T lymphocytes persist in the joints and have the characteristic of memory cells, meaning they retain their autoimmune properties long after the initial inflammatory response dies down, either spontaneously or after drug treatment,” ...
During a relapse of RA, joint inflammation often redevelops first in the same joints that were previously affected by disease. These particular memory T lymphocytes may explain this phenomenon ... The findings also suggest that the persistence of these memory lymphocytes is responsible for the continued, gradual joint destruction in many patients with RA who are in remission and feel well. ..."
From the significance and abstract:
"Significance
The significance of our presented work supports the notion that MIF-dependent, CD74+ memory T cells mediate the chronicity of rheumatoid synovitis and the preferential relapse of disease in previously involved joints. Targeting of the MIF/CD74 signaling pathway in T cells may be therapeutically beneficial, particularly in those individuals with high expression MIF alleles, which occur in approximately 20% of individuals.
Abstract
High expression alleles of the innate cytokine, macrophage migration inhibitory factor (MIF), are associated with the development or the severity of autoimmune inflammatory diseases, including rheumatoid arthritis.
Numerous studies support MIF’s role in activating inflammatory pathways and MIF inhibition reduces joint pathology in different experimental models of arthritis.
We examined the impact of gene deletion of MIF or its cognate receptor CD74 in the T cell–dependent model of collagen-induced arthritis (CIA) and observed the complete absence of arthritis development, suggesting an unforeseen role for MIF/CD74 signaling in the development of arthritogenic T cells.
While MIF has been shown in model systems to contribute to T cell activation by augmenting innate responses, fewer than 1% of T lineage cells express CD74 in naive spleens and lymph nodes, and its functional consequences in pathogenic T cell subpopulations have not been studied.
We found CD74+ T cells to expand during CIA and to increase in number within joint synovium, where they express an effector memory phenotype and recapitulate CIA development upon transfer into naive mice.
We further found evidence for the presence of CD74+ T cells in the circulation and joint synovium of patients with rheumatoid arthritis.
MIF-dependent, CD74+ T cells may contribute to the chronicity of rheumatoid synovitis and to disease relapse in previously inflamed joints."
Pathogenic role of MIF receptor (CD74) expressing T cells in inflammatory arthritis (no public access)
Apparently, Google is able to show some of the images from this PNAS research article, but only blurred (see below). This is not very nice! I have noticed this many times before with other research articles.
