Abstract | INTRODUCTION: METHODS: RESULTS: In PSC, IL-6 specifically triggered phosphorylation of STAT3 in CD4 + T cells and lead to enhanced production of interferon (IFN) gamma and interleukin (IL)-17A. Phospho-STAT3-positive CD4 + T cells correlated with systemic inflammation ( C-reactive protein serum levels). Combination of immunohistology and flow cytometry indicated that phospho-STAT3-positive cells were enriched in the peribiliary liver stroma and represented CD4 + T cells with prominent production of IFN gamma and IL-17A. JAK1/2 inhibitors blocked STAT3 phosphorylation and production of IFN gamma and IL-6, whereas IL-17A was apparently resistant to this inhibition. DISCUSSION: Our results demonstrate systemic and local activation of the IL-6/STAT3 pathway in PSC. Resistance of IL-17A to STAT3-targeted inhibition points to a more complex immune dysregulation beyond STAT3 activation.
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Authors | Leona Dold, Leonie Frank, Philipp Lutz, Dominik J Kaczmarek, Benjamin Krämer, Jacob Nattermann, Tobias J Weismüller, Vittorio Branchi, Marieta Toma, Maria Gonzalez-Carmona, Christian P Strassburg, Ulrich Spengler, Bettina Langhans |
Journal | Clinical and translational gastroenterology
(Clin Transl Gastroenterol)
Vol. 14
Issue 8
Pg. e00603
(08 01 2023)
ISSN: 2155-384X [Electronic] United States |
PMID | 37256725
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology. |
Chemical References |
- Cytokines
- Interleukin-17
- Interleukin-6
- STAT3 protein, human
- STAT3 Transcription Factor
- IL6 protein, human
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Topics |
- Humans
- Cholangitis, Sclerosing
- Cytokines
(metabolism)
- Inflammation
- Inflammatory Bowel Diseases
- Interleukin-17
(genetics, metabolism)
- Interleukin-6
(metabolism)
- STAT3 Transcription Factor
(genetics, metabolism)
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