The p38 mitogen-activated protein kinase signaling cascade in CD4 T cells |
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Authors: | Francis Dodeller Hendrik Schulze-Koops |
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Institution: | (1) Nikolaus Fiebiger Center for Molecular Medicine, Clinical Research Group III, and Department of Internal Medicine III, University of Erlangen-Nuremberg, Glueckstrasse 6, 91054 Erlangen, Germany; |
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Abstract: | Since the identification of the p38 mitogen-activated protein kinase (MAPK) as a key signal-transducing molecule in the expression
of the proinflammatory cytokine tumor necrosis factor (TNF) more than 10 years ago, huge efforts have been made to develop
inhibitors of p38 MAPK with the intent to modulate unwanted TNF activity in diseases such as autoimmune diseases or sepsis.
However, despite some anti-inflammatory effects in animal models, no p38 MAPK inhibitor has yet demonstrated clinical efficacy
in human autoimmune disorders. One possible reason for this paradox might relate to the fact that the p38 MAPK signaling cascade
is involved in the functional regulation of several different cell types that all contribute to the complex pathogenesis of
human autoimmune diseases. In particular, p38 MAPK has a multifaceted role in CD4 T cells that have been implicated in initiating
and driving sustained inflammation in autoimmune diseases, such as rheumatoid arthritis or systemic vasculitis. Here we review
recent advances in the understanding of the role of the p38 MAPK signaling cascade in CD4 T cells and the consequences that
its inhibition provokes in T cell functions in vitro and in vivo. These new data suggest that p38 MAPK inhibitors may elicit several unwanted effects in human autoimmune diseases but may
be useful for the treatment of allergic disorders. |
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