Several autoimmune diseases, including Crohn's disease, rheumatoid arthritis, and type I diabetes, are marked by formation of ectopic lymphoid organlike structures within the affected tissues. The contribution of such ectopic follicles to disease pathogenesis remains unexplored. The role of LTi cells or related inducer cells (such as those found in CPs) in these lesions has yet to be explored. Forced expression of CXCL13/BLC in pancreatic islet cells resulted in the local formation of lymphoid follicles, but this was independent of LTi cells, because follicles were also observed in RORY-/-mice ( and unpublished collaborative result). However, CXCL13 expression by stromal cells is induced by LT0R signaling. As LTi-like cells are the producers of LTap, this system may bypass the requirement for the cells. In autoimmune diseases, inflammatory stimuli may result in activation of LTi or CP-like cells, particularly in the intestine, and this could induce excessive follicle formation. Consistent with this notion, the number of ILFs is increased in dextran sulfate-induced colitis in mice  and also in Crohn's disease  and ulcerative colitis  in humans . Such tertiary lymphoid tissue could have a central role in autoimmune disease. Because nuclear receptors are readily amenable to pharmacological manipulation, inhibition of RORYt function in vivo may be achievable and may provide a means to control inflammatory bowel disease.
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