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TIM-4 Identifies Effector B Cells Expressing An IL-23-Driven Proinflammatory Cytokine Module That Promotes Immune Responses

Ding, Q;Wu, Y;Triglia, ET;Gommerman, JL;Subramanian, A;Kuchroo, VK;Rothstein, DM;

B cells can express pro-inflammatory cytokines that promote a wide variety of immune responses. Here we show that B cells expressing the phosphatidylserine receptor TIM-4, preferentially express not only IL-17A, but also IL-22, IL-6, and GM-CSF – a collection of cytokines reminiscent of pathogenic Th17 cells. Expression of this proinflammatory module requires B cell expression of IL-23R, ROR ?t and IL-17. IL-17 expressed by TIM-4 + B cells not only enhances the severity of experimental autoimmune encephalomyelitis (EAE) and promotes allograft rejection, but also acts in an autocrine manner to prevent their conversion into IL-10-expressing B cells with regulatory function. Thus, IL-17 acts as an inflammatory mediator and also enforces the proinflammatory activity of TIM-4 + B cells. TIM-4 serves as a broad marker for effector B cells (Beff) that will allow the study of the signals regulating their differentiation and expression of their effector molecules.