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IL-17A ≠ Th17 in GvHD

Cellular & Molecular Immunology volume 15, pages 282–283 (2018)Cite this article

In the current issue of Cellular & Molecular Immunology, Cai et al.1 demonstrate that IL-17A-producing CD4 T (Th17) cells induce graft-versus-host disease (GvHD), whereas the IL-17A cytokine is protective in GvHD after allogeneic bone marrow transplantation (allo-BMT). This study clarifies the role of Th17 cells and IL-17A in GvHD and identifies a valid concern about targeting Th17 cells via IL-17A blockade for GvHD prevention.

Th17 cells are derived from the CD4 T-cell lineage and can produce cytokines such as IL-17A, IL-17F, IL-21 and IL-22, among others. The combination of the cytokines TGFβ, IL-6 and IL-1β promotes Th17 cell differentiation, which requires the transcription factor RORγt. Th17 cells play an important role in host defense and in inflammation in autoimmune diseases.2 The pathogenicity of Th17 cells or IL-17A in GvHD has not been clearly defined. To study the role of Th17 cells in GvHD pathogenicity, genetic deficiency of RORγt or IL-17A was used to block Th17 cell differentiation. Yu et al.3 found that donor T cells deficient in RORγt had a normal ability to cause GvHD. By contrast, donor T cells deficient in both Tbet and RORγt exhibited an impaired ability to induce GvHD, as both Th1 and Th17 cell differentiation was blocked. However, by using RORγt−/− CD25− T cells, Fulton et al.4 demonstrated that impaired Th17 cell differentiation resulted in significantly attenuated GvHD, suggesting that RORγt deficiency may affect the function of regulatory T (Treg) cells. Similarly, Kappel et al.5 found that IL-17A−/− CD4 T cells, but not total T cells, exhibited a reduced ability to induce GvHD; this effect was associated with lower levels of IFNγ production by CD4 T cells, macrophages, and granulocytes during the early stage of BMT. By contrast, when Yi et al.6 transferred IL-17A−/− splenocytes or T cells into sub-lethally irradiated recipients, IL-17A deficiency augmented GvHD lethality and increased Th1 cell differentiation in recipients. They illustrated a protective role of IL-17A in the repression of Th1 cell differentiation by regulating host dendritic cells. Differences in the cytokine environment caused by different radiation intensities and different kinetics of GvHD development in different models of allo-BMT may affect whether Th17 cells and IL-17A play pro- or anti-inflammatory roles in GvHD.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, 29425, SC, USA

    Yongxia Wu & Xue-Zhong Yu

  2. Department of Medicine, Medical University of South Carolina, Charleston, 29425, SC, USA

    Xue-Zhong Yu

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Correspondence to Xue-Zhong Yu.

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Wu, Y., Yu, XZ. IL-17A ≠ Th17 in GvHD. Cell Mol Immunol 15, 282–283 (2018). https://doi.org/10.1038/cmi.2016.54

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