CD69 downregulates autoimmune reactivity through active transforming growth factor-β production in collagen-induced arthritis
David Sancho, … , Pilar Lauzurica, Francisco Sánchez-Madrid
David Sancho, … , Pilar Lauzurica, Francisco Sánchez-Madrid
Published September 15, 2003
Citation Information: J Clin Invest. 2003;112(6):872-882. https://doi.org/10.1172/JCI19112.
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CD69 downregulates autoimmune reactivity through active transforming growth factor-β production in collagen-induced arthritis

Abstract

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.

Authors

David Sancho, Manuel Gómez, Fernando Viedma, Enric Esplugues, Mónica Gordón-Alonso, María Angeles García-López, Hortensia de la Fuente, Carlos Martínez-A, Pilar Lauzurica, Francisco Sánchez-Madrid

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Figure 2

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Histological assessment of CIA in CD69-deficient mice. (a) Representativ...
Histological assessment of CIA in CD69-deficient mice. (a) Representative section of joint histopathology on whole paws of control (CFA, left panel, ×100) and CII-immunized CD69+/+ (middle panel, ×100) and CD69–/– (right panel, ×60) mice. Arrowheads indicate cartilage and bone erosions, and arrows indicate leukocyte infiltrates and pannus. C, cartilage; B, bone. (b) Scoring of inflammation, cartilage damage, pannus formation, and bone erosion of paws from CD69+/+ (white bars) and CD69–/– (black bars) mice as described in Methods. Results are expressed as the arithmetic mean ± SD of the percentage of joints ascribed to each severity group from three independent experiments (eight mice per group per experiment); *P < 0.01 versus CD69+/+ (Mann-Whitney U test).