Mark D. Okusa
University of Virginia Health Sciences Center, Charlottesville, Virginia, USA.
Phone: (434) 924-2187
Fax: (434) 924-5848
View the PDF of this article at: https://www.the-jci.org/press/15483.pdf
CD69 and TGF-beta: double trouble in arthritis
Francisco Snchez-Madrid and colleagues from Hospital de La Princesa in Madrid, Spain explored the role of the cytokine CD69 in a mouse model of collagen-induced arthritis (CIA). Their results strongly suggest that CD69 is a negative regulator of autoimmune reactivity and agonistic anti-CD69 antibodies may be useful in the treatment of chronic inflammation in diseases such as arthritis.
The CD69 receptor is induced following activation of leukocytes at inflammatory sites, but its physiological role during inflammation remains unknown. Snchez-Madrid and colleagues explored the role of CD69 in autoimmune reactivity by analyzing a model of CIA in CD69-deficient mice. CD69/ mice showed increased CIA, with exacerbated T and B cell immune responses to type II collagen. Transforming growth factor (TGF) -beta1 and TGF- beta2, which are protective in CIA, were reduced in the inflamed joints of CD69/ mice, correlating with the increase in other proinflammatory cytokines. Local injection of blocking antiTGF-beta antibodies increased CIA severity and proinflammatory cytokines in control but not CD69/ mice. These results show that CD69 is a negative modulator of autoimmune reactivity and inflammation through synthesis of TGF-beta, a cytokine that in turn downregulates the production of various proinflammatory mediators.
TITLE: CD69 downregulates autoimmune reactivity through active transforming growth factor-beta production in collagen-induced arthritis