Batf-dependent Th17 cells critically regulate IL-23 driven colitis-associated colon cancer

Punkenburg E, Vogler T, Büttner M, Amann KU, Waldner M, Atreya R, Abendroth B, Mudter J, Merkel S, Gallmeier E, Rose-John S, Neurath M, Hildner K (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Gut BMJ Publishing Group

Book Volume: 65

Pages Range: 1139-50

Journal Issue: 7

DOI: 10.1136/gutjnl-2014-308227

Abstract

IBDs have an increased risk for development of colorectal cancer (CRC). Here, we aimed at the characterisation of the functional role of Th17-associated transcription factors in sporadic and colitis-associated colon cancer in vivo.We used mice deficient or transgenic for the activating protein 1 family member basic leucine zipper transcription factor ATF-like (Batf) to evaluate the role of Th17 cells during sporadic and inflammation-induced colon carcinogenesis. We also studied the expression of Batf and ROR?t in patients with IBD and CRC.Batf but not retinoic acid-related orphan receptor ?t(ROR?t) expression was significantly increased together with interleukin (IL) 23 expression in UC but not in Crohn's disease (CD) tissue samples. In CRC also Batf but not ROR?t expression was increased and its expression correlated with the IL-23 and IL-23 receptor (IL-23R) expression. Finally, Batf but not ROR?t was coexpressed with IL-17a, IL-23R and IL-6 within CRC-infiltrating CD4(+) T cells. Functional studies in mice revealed that Batf-dependent T cells are crucial regulators of sporadic and inflammation-induced CRC. Colitis-associated Batf(-/-) tumours lacked IL-17a(+)IL-23R(+)IL-6(+)CD4(+) T cells, hence displaying characteristics reminiscent of human CRC-infiltrating CD4(+) T cells. Strikingly, Batf(-/-) tumours contained low IL-23 but high IL-17a expression levels. Tumour formation and intratumoral IL-23 expression could be restored by administration of Hyper-IL-6 consisting of IL-6 and soluble IL-6 receptor.Batf-dependent IL-23R(+)IL-6(+)CD4(+) Th17 cells critically control IL-23 driven colitis-associated tumour formation and the progression of sporadic colon tumours. Batf-dependent IL-23R(+) T cells represent a potential future therapeutic target limiting CRC progression.

Authors with CRIS profile

Elise Punkenburg Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Kerstin Ute Amann Professur für Nephropathologie Maximilian Waldner Lehrstuhl für Innere Medizin I Raja Atreya Professur für Translationale Immunforschung bei chronisch entzündlichen Darmerkrankungen (Heisenberg-Professur) Benjamin Abendroth Juniorprofessur für Pneumologie/ Immunologie Susanne Merkel Department of Surgery Markus Neurath Lehrstuhl für Innere Medizin I Kai Hildner Juniorprofessur für Pneumologie/ Immunologie

Involved external institutions

Sana Kliniken Ostholstein DE Germany (DE) Philipps-Universität Marburg DE Germany (DE) Christian-Albrechts-Universität zu Kiel DE Germany (DE)

How to cite

APA:

Punkenburg, E., Vogler, T., Büttner, M., Amann, K.U., Waldner, M., Atreya, R.,... Hildner, K. (2016). Batf-dependent Th17 cells critically regulate IL-23 driven colitis-associated colon cancer. Gut, 65(7), 1139-50. https://doi.org/10.1136/gutjnl-2014-308227

MLA:

Punkenburg, Elise, et al. "Batf-dependent Th17 cells critically regulate IL-23 driven colitis-associated colon cancer." Gut 65.7 (2016): 1139-50.

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