CCL2 recruitment of IL-6-producing CD11b+ monocytes to the draining lymph nodes during the initiation of Th17-dependent B cell-mediated autoimmunity
Ying Bai; Ruolan Liu; DeRen Huang; Antonio La Cava; Yi-yuan Tang; Yoichiro Iwakura; Denise I. Campagnolo; Timothy L. Vollmer; Richard M. Ransohoff; and Fu-Dong Shi
11/30/2013
Immunology
<p align="justify"><span style="line-height: 150%; font-family: Arial,sans-serif; font-size: 10pt">The development and function of Th17 cells are influenced in part by the cytokines TGF-ß, 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<sup>+ </sup>cells <em>via</em> 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 neuromuscula 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 <em>via </em>a novel mecahnism that involves CCL2.</span></p>