Comprehensive Intestinal T Helper Cell Profiling Reveals Specific Accumulation of IFN-γ+IL-17+Coproducing CD4+ T Cells in Active Inflammatory Bowel Disease (original) (raw)

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*Department of Medicine II

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*Department of Medicine II

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*Department of Medicine II

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†Institute for Clinical Pathology

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‡Department of Surgery, University Hospital of Freiburg, Freiburg, Germany

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*Department of Medicine II

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*Department of Medicine II

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*Department of Medicine II

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Published:

21 September 2014

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Anna-Maria Globig, Nadine Hennecke, Bianca Martin, Maximilian Seidl, Günther Ruf, Peter Hasselblatt, Robert Thimme, Bertram Bengsch, Comprehensive Intestinal T Helper Cell Profiling Reveals Specific Accumulation of IFN-γ+IL-17+Coproducing CD4+ T Cells in Active Inflammatory Bowel Disease, Inflammatory Bowel Diseases, Volume 20, Issue 12, 1 December 2014, Pages 2321–2329, https://doi.org/10.1097/MIB.0000000000000210
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Objective

Skewed T helper (TH) cell responses and specific functions of TH1, TH2, TH17, and Treg cells have been implicated in the pathogenesis of inflammatory bowel disease (IBD) that led to the establishment of the pathogenic TH1/TH2 and TH17/Treg cell imbalance paradigms. However, the relevant TH cell population driving mucosal inflammation is still unknown.

Methods

We performed a comprehensive TH cell profiling of circulating and intestinal lymphocytes isolated from patients with Crohn’s disease (CD; n = 69) and ulcerative colitis (UC; n = 41) undergoing endoscopy or surgical resection and compared them with healthy controls (n = 45). Mucosal inflammation was assessed endoscopically and histologically. TH cells were analyzed by flow cytometric evaluation of cytokine production and differentiation marker expression.

Results

Specialized TH cell populations were enriched in the intestinal mucosa compared with peripheral blood. Specifically, we observed a concomitant upregulation of TH17 cells and Tregs in active inflammatory lesions in patients with both CD and UC compared with quiescent/mildly inflamed lesions and healthy tissue. Of note, interferon γ+ interleukin (IL)-17+coproducing CD4+ T cells with high expression of T-bet, CD26, and IL-22 resembling recently described pathogenic TH17 cells were specifically enriched in the inflamed mucosal tissue.

Conclusions

Our results argue against the controversial TH1/TH2 or TH17/Treg paradigms. In contrast, they suggest that a subpopulation of TH17 cells sharing a TH1 signature may be specifically involved in intestinal inflammation in CD and UC. These findings provide a better understanding of IBD pathogenesis and may help explain the efficacy of anti-IL-12p40/IL-23 and failure of anti-IL-17A therapies despite the enrichment of TH17 cells.

Copyright © 2014 Crohn's & Colitis Foundation of America, Inc.

Topic:

• cytokine
• inflammation
• crohn's disease
• inflammatory bowel disease
• ulcerative colitis
• endoscopy
• dipeptidyl-peptidase iv
• intestinal mucosa
• intestines
• lymphocytes
• t-lymphocytes
• helper-inducer t-lymphocytes
• up-regulation (physiology)
• mucous membrane
• interleukin-22
• interleukin-23
• mucositis
• regulatory t-lymphocytes
• th17 cells
• t cell differentiation
• fluid flow

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