CCL2 recruitment of IL-6-producing CD11b+ monocytes to the draining lymph nodes during the initiation of Th17-dependent B cell-mediated autoimmunity.
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.
Bai
Ying
Y
Institute of Neuroinformatics and Laboratory for Brain and Mind, Dalian University of Technology, Dalian, China.
Liu
Ruolan
R
Huang
DeRen
D
La Cava
Antonio
A
Tang
Yi-yuan
YY
Iwakura
Yoichiro
Y
Campagnolo
Denise I
DI
Vollmer
Timothy L
TL
Ransohoff
Richard M
RM
Shi
Fu-Dong
FD
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
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