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CD69 downregulates autoimmune reactivity through active transforming growth factor-β production in collagen-induced arthritis

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dc.creator Sancho, David
dc.creator Gómez, Manuel
dc.creator Viedma, Fernando
dc.creator Esplugues, Enric
dc.creator Gordón Alonso, Mónica
dc.creator García López, María Ángeles
dc.creator Fuente, Hortensia de la
dc.creator Martínez-Alonso, Carlos
dc.creator Lauzurica, Pilar
dc.creator Sánchez-Madrid, Francisco
dc.date 2008-04-16T07:42:01Z
dc.date 2008-04-16T07:42:01Z
dc.date 2003-09
dc.date.accessioned 2017-01-31T01:02:20Z
dc.date.available 2017-01-31T01:02:20Z
dc.identifier The Journal of Clinical Investigation, September 2003, Volume 112, Number 6. pp. 872-882
dc.identifier 0021-9738
dc.identifier http://hdl.handle.net/10261/3602
dc.identifier 10.1172/JCI200319112.
dc.identifier.uri http://dspace.mediu.edu.my:8181/xmlui/handle/10261/3602
dc.description CD69 is induced after activation of leukocytes at inflammatory sites, but its physiological role during inflammation remains unknown. We explored the role of CD69 in autoimmune reactivity by analyzing a model of collagen-induced arthritis (CIA) in WT and CD69-deficient mice. CD69–/– mice showed higher incidence and severity of CIA, with exacerbated T and B cell immune responses to type II collagen. Levels of TGF-β1 and TGF-β2, which act as protective agents in CIA, were reduced in CD69–/– mice inflammatory foci, correlating with the increase in the proinflammatory cytokines IL-1β and RANTES. Local injection of blocking anti–TGF-β antibodies increased CIA severity and proinflammatory cytokine mRNA levels in CD69+/+ but not in CD69–/– mice. Moreover, in vitro engagement of CD69 induced total and active TGF-β1 production in Concanavalin A–activated splenocyte subsets, mouse and human synovial leukocytes, and Jurkat stable transfectants of human CD69 but not in the parental CD69 negative cell line. Our results show that CD69 is a negative modulator of autoimmune reactivity and inflammation through the synthesis of TGF-β, a cytokine that in turn downregulates the production of various proinflammatory mediators.
dc.description Peer reviewed
dc.format 2945546 bytes
dc.format application/pdf
dc.language eng
dc.publisher American Society for Clinical Investigation
dc.rights openAccess
dc.title CD69 downregulates autoimmune reactivity through active transforming growth factor-β production in collagen-induced arthritis
dc.type Artículo


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