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2 results on '"Steglich B"'

1. Tissue resident iNKT17 cells facilitate cancer cell extravasation in liver metastasis via interleukin-22.

Author

Giannou AD, Kempski J, Shiri AM, Lücke J, Zhang T, Zhao L, Zazara DE, Cortesi F, Riecken K, Amezcua Vesely MC, Low JS, Xu H, Kaffe E, Garcia-Perez L, Agalioti T, Yamada Y, Jungraithmayr W, Zigmond E, Karstens KF, Steglich B, Wagner J, Konczalla L, Carambia A, Schulze K, von Felden J, May P, Briukhovetska D, Bedke T, Brockmann L, Starzonek S, Lange T, Koch C, Riethdorf S, Pelczar P, Böttcher M, Sabihi M, Huber FJ, Reeh M, Grass JK, Wahib R, Seese H, Stüben BO, Fard-Aghaie M, Duprée A, Scognamiglio P, Plitzko G, Meiners J, Soukou S, Wittek A, Manthey C, Maroulis IC, Arck PC, Perez D, Gao B, Zarogiannis SG, Strowig T, Pasqualini R, Arap W, Gosálvez JS, Kobold S, Prinz I, Guse AH, Tachezy M, Ghadban T, Heumann A, Li J, Melling N, Mann O, Izbicki JR, Pantel K, Schumacher U, Lohse AW, Flavell RA, Gagliani N, and Huber S

Subjects
Animals, Mice, Endothelial Cells metabolism, Mice, Inbred C57BL, Colorectal Neoplasms metabolism, Interleukin-22, Interleukins metabolism, Liver Neoplasms pathology, Liver Neoplasms secondary, Natural Killer T-Cells metabolism
Abstract

During metastasis, cancer cells invade, intravasate, enter the circulation, extravasate, and colonize target organs. Here, we examined the role of interleukin (IL)-22 in metastasis. Immune cell-derived IL-22 acts on epithelial tissues, promoting regeneration and healing upon tissue damage, but it is also associated with malignancy. Il22-deficient mice and mice treated with an IL-22 antibody were protected from colon-cancer-derived liver and lung metastasis formation, while overexpression of IL-22 promoted metastasis. Mechanistically, IL-22 acted on endothelial cells, promoting endothelial permeability and cancer cell transmigration via induction of endothelial aminopeptidase N. Multi-parameter flow cytometry and single-cell sequencing of immune cells isolated during cancer cell extravasation into the liver revealed iNKT17 cells as source of IL-22. iNKT-cell-deficient mice exhibited reduced metastases, which was reversed by injection of wild type, but not Il22-deficient, invariant natural killer T (iNKT) cells. IL-22-producing iNKT cells promoting metastasis were tissue resident, as demonstrated by parabiosis. Thus, IL-22 may present a therapeutic target for prevention of metastasis., Competing Interests: Declaration of interests S.K. declares honoraria from GSK, BMS, Novartis, and TCR2, Inc.; license fees from TCR2, Inc. and Carina Biotech; and research support from TCR2, Inc., Plectonic GmbH, Tabby Therapeutics, and Arcus Biosciences., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2023
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2. TGF-β signaling in Th17 cells promotes IL-22 production and colitis-associated colon cancer.

Author

Perez LG, Kempski J, McGee HM, Pelzcar P, Agalioti T, Giannou A, Konczalla L, Brockmann L, Wahib R, Xu H, Vesely MCA, Soukou S, Steglich B, Bedke T, Manthey C, Seiz O, Diercks BP, Gnafakis S, Guse AH, Perez D, Izbicki JR, Gagliani N, Flavell RA, and Huber S

Subjects
Animals, Basic Helix-Loop-Helix Transcription Factors genetics, Basic Helix-Loop-Helix Transcription Factors metabolism, Carcinogenesis immunology, Cell Differentiation, Colitis immunology, Colonic Neoplasms immunology, Colonic Neoplasms pathology, Colorectal Neoplasms etiology, Colorectal Neoplasms immunology, Colorectal Neoplasms pathology, Disease Models, Animal, Female, Humans, Interleukin-17 genetics, Interleukin-17 metabolism, Lymphocytes, Tumor-Infiltrating immunology, Lymphocytes, Tumor-Infiltrating pathology, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Phosphatidylinositol 3-Kinases metabolism, Receptors, Aryl Hydrocarbon genetics, Receptors, Aryl Hydrocarbon metabolism, Signal Transduction immunology, Th17 Cells pathology, Transforming Growth Factor beta1 metabolism, Interleukin-22, Colitis complications, Colonic Neoplasms etiology, Interleukins biosynthesis, Th17 Cells immunology, Transforming Growth Factor beta metabolism
Abstract

IL-22 has dual functions during tumorigenesis. Short term IL-22 production protects against genotoxic stress, whereas uncontrolled IL-22 activity promotes tumor growth; therefore, tight regulation of IL-22 is essential. TGF-β1 promotes the differentiation of Th17 cells, which are known to be a major source of IL-22, but the effect of TGF-β signaling on the production of IL-22 in CD4+ T cells is controversial. Here we show an increased presence of IL-17+IL-22+ cells and TGF-β1 in colorectal cancer compared to normal adjacent tissue, whereas the frequency of IL-22 single producing cells is not changed. Accordingly, TGF-β signaling in CD4+ T cells (specifically Th17 cells) promotes the emergence of IL-22-producing Th17 cells and thereby tumorigenesis in mice. IL-22 single producing T cells, however, are not dependent on TGF-β signaling. We show that TGF-β, via AhR induction, and PI3K signaling promotes IL-22 production in Th17 cells.

Published
2020
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