title: CCL2 recruitment of IL-6-producing CD11b+ monocytes to the draining lymph nodes during the initiation of Th17-dependent B cell-mediated autoimmunity.
abstract: The development and function of Th17 cells are influenced in part by the cytokines TGF-beta, IL-23 and IL-6, but the mechanisms that govern recruitment and activity of Th17 cells during initiation of autoimmunity remain poorly defined. We show here that the development of autoreactive Th17 cells in secondary lymphoid organs in experimental autoimmune myasthenia gravis--an animal model of human myasthenia gravis--is modulated by IL-6-producing CD11b(+) cells via the CC chemokine ligand 2 (CCL2). Notably, acetylcholine receptor (AChR)-reactive Th17 cells provide help for the B cells to produce anti-AChR antibodies, which are responsible for the impairment of the neuromuscular transmission that contributes to the clinical manifestations of autoimmunity, as indicated by a lack of disease induction in IL-17-deficient mice. Thus, Th17 cells can promote humoral autoimmunity via a novel mechanism that involves CCL2.
authors.affiliation: Institute of Neuroinformatics and Laboratory for Brain and Mind, Dalian University of Technology, Dalian, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Bai
authors.forename: Ruolan
authors.initials: R
authors.lastname: Liu
authors.forename: DeRen
authors.initials: D
authors.lastname: Huang
authors.forename: Antonio
authors.initials: A
authors.lastname: La Cava
authors.forename: Yi-yuan
authors.initials: YY
authors.lastname: Tang
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Denise I
authors.initials: DI
authors.lastname: Campagnolo
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Vollmer
authors.forename: Richard M
authors.initials: RM
authors.lastname: Ransohoff
authors.forename: Fu-Dong
authors.initials: FD
authors.lastname: Shi
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D039481:CD11b Antigen / Q000276:immunology / Q000378:metabolism; D018932:Chemokine CCL2 / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D020381:Interleukin-17 / Q000276:immunology; D053759:Interleukin-23 / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism*; D008198:Lymph Nodes / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D039481:CD11b Antigen; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D020381:Interleukin-17; D053759:Interleukin-23; D015850:Interleukin-6; D011950:Receptors, Cholinergic; D016212:Transforming Growth Factor beta