For over 35 years, immunologists have divided T-helper (TH) cells into functional subsets. T-helper type 1 (TH1) cells—long thought to mediate tissue damage—might be involved in the initiation of damage, but they do not sustain or play a decisive role in many commonly studied models of autoimmunity, allergy and microbial immunity. A major role for the cytokine interleukin-17 (IL-17) has now been described in various models of immune-mediated tissue injury, including organ-specific autoimmunity in the brain, heart, synovium and intestines, allergic disorders of the lung and skin, and microbial infections of the intestines and the nervous system. A pathway named TH17 is now credited for causing and sustaining tissue damage in these diverse situations. The TH1 pathway antagonizes the TH17 pathway in an intricate fashion. The evolution of our understanding of the TH17 pathway illuminates a shift in immunologists' perspectives regarding the basis of tissue damage, where for over 20 years the role of TH1 cells was considered paramount.
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NOTE: In the version of this article initially published, the labeling in Figure 1 is incorrect. Tregs should be shown as producing TGF-β, not IL-17. The error has been corrected in the HTML and PDF versions of the article.
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I thank R. Coffman and T. Mosmann, whose work inspired this review, for their constructive comments. I appreciate the input from H. Cantor, A. Zlotnik and Lee and Len Herzenberg.
The author declares no competing financial interests.
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Steinman, L. A brief history of TH17, the first major revision in the TH1/TH2 hypothesis of T cell–mediated tissue damage. Nat Med 13, 139–145 (2007). https://doi.org/10.1038/nm1551
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