4 results on '"Brockmann, Leonie"'
Search Results
2. Th17 cells transdifferentiate into regulatory T cells during resolution of inflammation
- Author
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Gagliani, Nicola, Vesely, Maria Carolina Amezcua, Iseppon, Andrea, Brockmann, Leonie, Xu, Hao, Palm, Noah W, de Zoete, Marcel R, Licona-Limón, Paula, Paiva, Ricardo S, Ching, Travers, Weaver, Casey, Zi, Xiaoyuan, Pan, Xinghua, Fan, Rong, Garmire, Lana X, Cotton, Matthew J, Drier, Yotam, Bernstein, Bradley, Geginat, Jens, Stockinger, Brigitta, Esplugues, Enric, Huber, Samuel, Flavell, Richard A, LS Infectiebiologie (Bacteriologie), I&I SIB2, Infection & Immunity, LS Infectiebiologie (Bacteriologie), I&I SIB2, and Infection & Immunity
- Subjects
Male ,Staphylococcus aureus ,medicine.medical_treatment ,T-Lymphocytes ,Helminthiasis ,Inflammation ,Biology ,T-Lymphocytes, Regulatory ,Article ,Mice ,Immune system ,Cell Plasticity ,medicine ,Animals ,Multidisciplinary ,Gene Expression Profiling ,Transdifferentiation ,T helper cell ,Staphylococcal Infections ,Regulatory ,Cell biology ,Cytokine ,medicine.anatomical_structure ,Gene Expression Regulation ,Cell Transdifferentiation ,Immunology ,Th17 Cells ,Female ,Nippostrongylus ,medicine.symptom ,Reprogramming - Abstract
Inflammation is a beneficial host response to infection but can contribute to inflammatory disease if unregulated. The TH17 lineage of T helper (TH) cells can cause severe human inflammatory diseases. These cells exhibit both instability (they can cease to express their signature cytokine, IL-17A)1 and plasticity (they can start expressing cytokines typical of other lineages)1,2 upon in vitro re-stimulation. However, technical limitations have prevented the transcriptional profiling of pre- and post-conversion TH17 cells ex vivo during immune responses. Thus, it is unknown whether TH17 cell plasticity merely reflects change in expression of a few cytokines, or if TH17 cells physiologically undergo global genetic reprogramming driving their conversion from one T helper cell type to another, a process known as transdifferentiation3,4. Furthermore, although TH17 cell instability/plasticity has been associated with pathogenicity1,2,5, it is unknown whether this could present a therapeutic opportunity, whereby formerly pathogenic TH17 cells could adopt an anti-inflammatory fate. Here we used two new fate-mapping mouse models to track TH17 cells during immune responses to show that CD4+ T cells that formerly expressed IL-17A go on to acquire an anti-inflammatory phenotype. The transdifferentiation of TH17 into regulatory T cells was illustrated by a change in their signature transcriptional profile and the acquisition of potent regulatory capacity. Comparisons of the transcriptional profiles of pre- and postconversion TH17 cells also revealed a role for canonical TGF-β signalling and consequently for the aryl hydrocarbon receptor (AhR) in conversion. Thus, TH17 cells transdifferentiate into regulatory cells, and contribute to the resolution of inflammation. Our data suggest that TH17 cell instability and plasticity is a therapeutic opportunity for inflammatory diseases.
- Published
- 2015
3. CD4+ T-cell-derived IL-10 promotes CNS inflammation in mice by sustaining effector T cell survival.
- Author
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Yogev, Nir, Bedke, Tanja, Kobayashi, Yasushi, Brockmann, Leonie, Lukas, Dominika, Regen, Tommy, Croxford, Andrew L., Nikolav, Alexei, Hövelmeyer, Nadine, von Stebut, Esther, Prinz, Marco, Ubeda, Carles, Maloy, Kevin J., Gagliani, Nicola, Flavell, Richard A., Waisman, Ari, and Huber, Samuel
- Abstract
Interleukin (IL)-10 is considered a prototypical anti-inflammatory cytokine, significantly contributing to the maintenance and reestablishment of immune homeostasis. Accordingly, it has been shown in the intestine that IL-10 produced by Tregs can act on effector T cells, thereby limiting inflammation. Herein, we investigate whether this role also applies to IL-10 produced by T cells during central nervous system (CNS) inflammation. During neuroinflammation, both CNS-resident and -infiltrating cells produce IL-10; yet, as IL-10 has a pleotropic function, the exact contribution of the different cellular sources is not fully understood. We find that T-cell-derived IL-10, but not other relevant IL-10 sources, can promote inflammation in experimental autoimmune encephalomyelitis. Furthermore, in the CNS, T-cell-derived IL-10 acts on effector T cells, promoting their survival and thereby enhancing inflammation and CNS autoimmunity. Our data indicate a pro-inflammatory role of T-cell-derived IL-10 in the CNS. [Display omitted] • IL-10 can promote pro-inflammatory responses • T cells are the key source of pro-inflammatory IL-10 • IL-10 exerts its pro-inflammatory function by acting on effector T cells • IL-10 promotes effector T cell survival Yogev et al. report that IL-10 is not only anti-inflammatory but also has an important pro-inflammatory function. T-cell-derived IL-10 regulates the survival of pro-inflammatory T cells and contributes to the development of central nervous system autoimmunity. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
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4. IL22BP Mediates the Antitumor Effects of Lymphotoxin Against Colorectal Tumors in Mice and Humans.
- Author
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Kempski, Jan, Giannou, Anastasios D., Riecken, Kristoffer, Zhao, Lilan, Steglich, Babett, Lücke, Jöran, Garcia-Perez, Laura, Karstens, Karl-Frederick, Wöstemeier, Anna, Nawrocki, Mikolaj, Pelczar, Penelope, Witkowski, Mario, Nilsson, Sven, Konczalla, Leonie, Shiri, Ahmad Mustafa, Kempska, Joanna, Wahib, Ramez, Brockmann, Leonie, Huber, Philipp, and Gnirck, Ann-Christin
- Abstract
Unregulated activity of interleukin (IL) 22 promotes intestinal tumorigenesis in mice. IL22 binds the antagonist IL22 subunit alpha 2 (IL22RA2, also called IL22BP). We studied whether alterations in IL22BP contribute to colorectal carcinogenesis in humans and mice. We obtained tumor and nontumor tissues from patients with colorectal cancer (CRC) and measured levels of cytokines by quantitative polymerase chain reaction, flow cytometry, and immunohistochemistry. We measured levels of Il22bp messenger RNA in colon tissues from wild-type, Tnf
–/– , Lta–/– , and Ltb–/– mice. Mice were given azoxymethane and dextran sodium sulfate to induce colitis and associated cancer or intracecal injections of MC38 tumor cells. Some mice were given inhibitors of lymphotoxin beta receptor (LTBR). Intestine tissues were analyzed by single-cell sequencing to identify cell sources of lymphotoxin. We performed immunohistochemistry analysis of colon tissue microarrays from patients with CRC (1475 tissue cores, contained tumor and nontumor tissues) and correlated levels of IL22BP with patient survival times. Levels of IL22BP were decreased in human colorectal tumors, compared with nontumor tissues, and correlated with levels of lymphotoxin. LTBR signaling was required for expression of IL22BP in colon tissues of mice. Wild-type mice given LTBR inhibitors had an increased tumor burden in both models, but LTBR inhibitors did not increase tumor growth in Il22bp–/– mice. Lymphotoxin directly induced expression of IL22BP in cultured human monocyte–derived dendritic cells via activation of nuclear factor κB. Reduced levels of IL22BP in colorectal tumor tissues were associated with shorter survival times of patients with CRC. Lymphotoxin signaling regulates expression of IL22BP in colon; levels of IL22BP are reduced in human colorectal tumors, associated with shorter survival times. LTBR signaling regulates expression of IL22BP in colon tumors in mice and cultured human dendritic cells. Patients with colorectal tumors that express low levels of IL22BP might benefit from treatment with an IL22 antagonist. [ABSTRACT FROM AUTHOR]- Published
- 2020
- Full Text
- View/download PDF
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