title: CD69 downregulates autoimmune reactivity through active transforming growth factor-beta 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-beta1 and TGF-beta2, which act as protective agents in CIA, were reduced in CD69-/- mice inflammatory foci, correlating with the increase in the proinflammatory cytokines IL-1beta and RANTES. Local injection of blocking anti-TGF-beta 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-beta1 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-beta, a cytokine that in turn downregulates the production of various proinflammatory mediators.
authors.affiliation: Servicio de Inmunología, Hospital de La Princesa, C/ Diego de León 62, E-28006 Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Sancho
authors.forename: Manuel
authors.initials: M
authors.lastname: Gómez
authors.forename: Fernando
authors.initials: F
authors.lastname: Viedma
authors.forename: Enric
authors.initials: E
authors.lastname: Esplugues
authors.forename: Mónica
authors.initials: M
authors.lastname: Gordón-Alonso
authors.forename: María Angeles
authors.initials: MA
authors.lastname: García-López
authors.forename: Hortensia
authors.initials: H
authors.lastname: de la Fuente
authors.forename: Carlos
authors.initials: C
authors.lastname: Martínez-A
authors.forename: Pilar
authors.initials: P
authors.lastname: Lauzurica
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez-Madrid
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001169:Arthritis, Experimental / Q000276:immunology / Q000378:metabolism*; D015551:Autoimmunity / Q000502:physiology*; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation; D005528:Foot / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007596:Joints / Q000166:cytology / Q000473:pathology; D037181:Lectins, C-Type; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013154:Spleen / Q000166:cytology / Q000473:pathology; D013582:Synovial Fluid / Q000166:cytology / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism*; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; D037181:Lectins, C-Type; D016212:Transforming Growth Factor beta; D000099192:CD69 Antigens