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Costimulation of Th17 cells: adding fuel or putting out the fire in the inflamed gut?

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Abstract

Inflammatory bowel disease, typified by Crohn’s disease and ulcerative colitis, is a common disorder characterized by recurrent and serious inflammation of the gastrointestinal tract. It is well documented that T cells play a pivotal role in the development of inflammatory bowel disease. Th17 cells are a unique T cell subpopulation implicated in inflammatory bowel disease and many other autoimmune/inflammatory diseases. However, the regulatory mechanism of Th17 activation and proliferation has not been defined completely. Recent studies have shown that the ligation of several costimulatory receptor–ligand pairs contributes to the activation, differentiation, and proliferation of T lymphocytes including the Th17 subset. In this review, we will discuss the emerging evidence on the role of Th17 cells in inflammatory bowel disease pathogenesis as well as the effect of costimulatory molecules on Th17 development and consider if the need for such costimulation of T lymphocytes provides a target for the development of novel therapeutic strategy.

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Acknowledgments

We thank Judie McDonald for help in preparing the manuscript. This study was supported by National Institutes of Health Grants HD033703-10 (ZZ), EY016788 (ZZ), EY013093 (JTR), and EY006484 (JTR) as well as Child Digestive Health and Nutrition Foundation/CCFA Young Investigator Award (ZZ). JTR is a scholar supported by Research to Prevent Blindness. Funds from the Stan and Madelle Rosenfeld Family Trust and the Kuzell Family Arthritis Research Foundation also contributed to this work.

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Authors and Affiliations

  1. Department of Pediatrics, Oregon Health & Science University, 707 Gaines St, CDRC, Portland, OR, 97239, USA

    Zili Zhang & Wenwei Zhong

  2. Departments of Internal Medicine and Ophthalmology, Oregon Health & Science University, 3181 SW Sam Jackson St, Portland, OR, 97239, USA

    James T. Rosenbaum

  3. Department of Internal Medicine, Oregon Health & Science University, 3181 SW Sam Jackson St, Portland, OR, 97239, USA

    Carmen Lim

  4. Portland VA Medical Center, 3710 SW US Veterans Hospital Rd, Portland, OR, 97239, USA

    David J. Hinrichs

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  1. Zili Zhang
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  2. James T. Rosenbaum
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  3. Wenwei Zhong
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Correspondence to Zili Zhang.

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Zhang, Z., Rosenbaum, J.T., Zhong, W. et al. Costimulation of Th17 cells: adding fuel or putting out the fire in the inflamed gut?. Semin Immunopathol 32, 55–70 (2010). https://doi.org/10.1007/s00281-009-0190-3

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  • DOI: https://doi.org/10.1007/s00281-009-0190-3

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