Journal article
STAT6 and Furin Are Successive Triggers for the Production of TGF-β by T Cells
The Journal of immunology (1950), Vol.201(9), pp.2612-2623
11/01/2018
DOI: 10.4049/jimmunol.1700808
PMCID: PMC6200631
PMID: 30266770
Abstract
Production of TGF-β by T cells is key to various aspects of immune homeostasis, with defects in this process causing or aggravating immune-mediated disorders. The molecular mechanisms that lead to TGF-β generation by T cells remain largely unknown. To address this issue, we take advantage of the fact that intestinal helminths stimulate Th2 cells besides triggering TGF-β generation by T lymphocytes and regulate immune-mediated disorders. We show that the Th2 cell-inducing transcription factor STAT6 is necessary and sufficient for the expression of TGF-β propeptide in T cells. STAT6 is also necessary for several helminth-triggered events in mice, such as TGF-β-dependent suppression of alloreactive inflammation in graft-versus-host disease. Besides STAT6, helminth-induced secretion of active TGF-β requires cleavage of propeptide by the endopeptidase furin. Thus, for the immune regulatory pathway necessary for TGF-β production by T cells, our results support a two-step model, composed of STAT6 and furin.
Details
- Title: Subtitle
- STAT6 and Furin Are Successive Triggers for the Production of TGF-β by T Cells
- Creators
- Yue Li - Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242Weiren Liu - Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242Xiaqun Guan - Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242Jamie Truscott - Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242John W Creemers - Laboratory for Biochemical Neuroendocrinology, Department of Human Genetics, KU Leuven, Leuven, B-3000 BelgiumHung-Lin Chen - Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242Marko Pesu - Department of Dermatology, Tampere University Hospital, FI-33520 Tampere, FinlandRami G El Abiad - Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242Bahri Karacay - Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242Joseph F Urban Jr - Diet, Genomics and Immunology Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705David E Elliott - Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242Mark H Kaplan - Department of Pediatrics, Herman B. Wells Center for Pediatric Research and Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202Bruce R Blazar - Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455; andM Nedim Ince - Holden Comprehensive Cancer Center, Carver College of Medicine, University of Iowa, Iowa City, IA 52242
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.201(9), pp.2612-2623
- DOI
- 10.4049/jimmunol.1700808
- PMID
- 30266770
- PMCID
- PMC6200631
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Publisher
- United States
- Grant note
- R01 AI034495 / NIAID NIH HHS R56 AI116715 / NIAID NIH HHS R01 HL095791 / NHLBI NIH HHS I01 BX002906 / BLRD VA R01 AI095282 / NIAID NIH HHS I01 BX002715 / BLRD VA U19 AI051731 / NIAID NIH HHS R01 HL056067 / NHLBI NIH HHS R37 AI034495 / NIAID NIH HHS
- Language
- English
- Date published
- 11/01/2018
- Academic Unit
- Stead Family Department of Pediatrics; Gastroenterology and Hepatology; Iowa Neuroscience Institute; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984065740002771
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