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IL-17-producing T helper (Th17) cells have been implicated in the pathogenesis of many inflammatory and autoimmune diseases. Targeting the effector cytokines IL-17 and GM-CSF secreted by autoimmune Th17 cells has been shown to be effective for the treatment of the diseases. Understanding a molecular basis of Th17 differentiation and effector functions is therefore critical for the regulation of the pathogenicity of tissue Th17 cells in chronic inflammation. Here, we discuss the roles of proinflammatory cytokines and environmental stimuli in the control of Th17 differentiation and chronic tissue inflammation by pathogenic Th17 cells in humans and in mouse models of autoimmune diseases. We also highlight recent advances in the regulation of pathogenic Th17 cells by gut microbiota and immunometabolism in autoimmune arthritis. [ABSTRACT FROM AUTHOR]

Tumour necrosis factor inhibitors (TNFi) have led to a paradigm shift in the treatment for various diseases including rheumatoid arthritis (RA). During the course of treatment, however, they sometimes cause adverse autoimmune disorders such as lupus, psoriasis and vasculitis. Here, we report a case in which a patient with RA under etanercept (ETN) treatment developed simultaneous ulcerations and blisters on the extremities. Skin biopsies showed leucocytoclastic vasculitis (LCV) at the ulcerative lesion, and subepidermal blistering with linear deposits of IgG and C3 at the basement membrane zone of the blister suggesting a pemphigoid disease. Such simultaneous development of LCV and pemphigoid in an RA patient has not previously been reported. We reviewed 71 cases of vasculitis and 7 cases of pemphigoid diseases during anti-TNF therapy. The prevalence of pemphigoids in RA patients appeared to be comparable to that in healthy individuals. This case showed that TNFi treatment may be involved in two distinct autoimmune reactions, in which vasculitis is related to the augmentation of pemphigoid. [ABSTRACT FROM AUTHOR]