Zfp362 potentiates murine colonic inflammation by constraining Treg cell function rather than promoting Th17 cell differentiation

被引:3
作者
Herppich, Susanne [1 ]
Hoenicke, Lisa [1 ]
Kern, Fabian [2 ,3 ]
Kruse, Friederike [1 ]
Smout, Justine [1 ]
Greweling-Pils, Marina C. [4 ,5 ]
Geffers, Robert
Burton, Oliver T. [6 ]
Liston, Adrian [6 ]
Keller, Andreas [2 ,3 ]
Floess, Stefan [1 ]
Huehn, Jochen [1 ]
机构
[1] Helmholtz Ctr Infect Res, Dept Expt Immunol, Braunschweig, Germany
[2] Saarland Univ, Helmholtz Inst Pharmaceut Res Saarland, Helmholtz Ctr Infect Res, Saarbrucken, Germany
[3] Saarland Univ, Dept Clin Bioinformat, Homburg, Germany
[4] Helmholtz Ctr Infect Res, Mouse Pathol Platform, Braunschweig, Germany
[5] Helmholtz Ctr Infect Res, Genome Analyt, Braunschweig, Germany
[6] Babraham Inst, Lab Lymphocyte Signalling & Dev, Cambridge, England
关键词
Zfp362; Th17; Treg cell; Intestinal Immunity; Mucosal inflammation; REGULATORY T-CELLS; PROINFLAMMATORY IL-17(+); INDUCTION; MECHANISMS; MICROBIOTA; EXPRESSION; PROGRAM; LINEAGE; FOXP3; MICE;
D O I
10.1002/eji.202250270
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Mucosal barrier integrity and pathogen clearance is a complex process influenced by both Th17 and Treg cells. Previously, we had described the DNA methylation profile of Th17 cells and identified Zinc finger protein (Zfp)362 to be uniquely demethylated. Here, we generated Zfp362(-/-) mice to unravel the role of Zfp362 for Th17 cell biology. Zfp362(-/-) mice appeared clinically normal, showed no phenotypic alterations in the T-cell compartment, and upon colonization with segmented filamentous bacteria, no effect of Zfp362 deficiency on Th17 cell differentiation was observed. By contrast, Zfp362 deletion resulted in increased frequencies of colonic Foxp3(+) Treg cells and IL-10(+) and ROR & gamma;t(+) Treg cell subsets in mesenteric lymph nodes. Adoptive transfer of naive CD4(+) T cells from Zfp362(-/-) mice into Rag2(-/-) mice resulted in a significantly lower weight loss when compared with controls receiving cells from Zfp362(+/+) littermates. However, this attenuated weight loss did not correlate with alterations of Th17 cells but instead was associated with an increase of effector Treg cells in mesenteric lymph nodes. Together, these results suggest that Zfp362 plays an important role in promoting colonic inflammation; however, this function is derived from constraining the effector function of Treg cells rather than directly promoting Th17 cell differentiation.
引用
收藏
页数:15
相关论文
共 56 条
[1]   Regulatory T Cells Reinforce Intestinal Homeostasis [J].
Barnes, Michael J. ;
Powrie, Fiona .
IMMUNITY, 2009, 31 (03) :401-411
[2]   COMMENSAL MICROBIOTA DRIVE PROLIFERATION OF CONVENTIONAL AND Foxp3(+) REGULATORY CD4(+) T CELLS IN MESENTERIC LYMPH NODES AND PEYER'S PATCHES [J].
Cording, Sascha ;
Fleissner, Diana ;
Heimesaat, Markus M. ;
Bereswill, Stefan ;
Loddenkemper, Christoph ;
Uematsu, Satoshi ;
Akira, Shizuo ;
Hamann, Alf ;
Huehn, Jochen .
EUROPEAN JOURNAL OF MICROBIOLOGY AND IMMUNOLOGY, 2013, 3 (01) :1-10
[3]   Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) [J].
Cossarizza, Andrea ;
Chang, Hyun-Dong ;
Radbruch, Andreas ;
Abrignani, Sergio ;
Addo, Richard ;
Akdis, Muebeccel ;
Andrae, Immanuel ;
Andreata, Francesco ;
Annunziato, Francesco ;
Arranz, Eduardo ;
Bacher, Petra ;
Bari, Sudipto ;
Barnaba, Vincenzo ;
Barros-Martins, Joana ;
Baumjohann, Dirk ;
Beccaria, Cristian G. ;
Bernardo, David ;
Boardman, Dominic A. ;
Borger, Jessica ;
Boettcher, Chotima ;
Brockmann, Leonie ;
Burns, Marie ;
Busch, Dirk H. ;
Cameron, Garth ;
Cammarata, Ilenia ;
Cassotta, Antonino ;
Chang, Yinshui ;
Chirdo, Fernando Gabriel ;
Christakou, Eleni ;
Cicin-Sain, Luka ;
Cook, Laura ;
Corbett, Alexandra J. ;
Cornelis, Rebecca ;
Cosmi, Lorenzo ;
Davey, Martin S. ;
De Biasi, Sara ;
De Simone, Gabriele ;
del Zotto, Genny ;
Delacher, Michael ;
Di Rosa, Francesca ;
Di Santo, James ;
Diefenbach, Andreas ;
Dong, Jun ;
Doerner, Thomas ;
Dress, Regine J. ;
Dutertre, Charles-Antoine ;
Eckle, Sidonia B. G. ;
Eede, Pascale ;
Evrard, Maximilien ;
Falk, Christine S. .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2021, 51 (12) :2708-3145
[4]   Single-cell chromatin accessibility landscape identifies tissue repair program in human regulatory T cells [J].
Delacher, Michael ;
Simon, Malte ;
Sanderink, Lieke ;
Hotz-Wagenblatt, Agnes ;
Wuttke, Marina ;
Schambeck, Kathrin ;
Schmidleithner, Lisa ;
Bittner, Sebastian ;
Pant, Asmita ;
Ritter, Uwe ;
Hehlgans, Thomas ;
Riegel, Dania ;
Schneider, Verena ;
Groeber-Becker, Florian Kai ;
Eigenberger, Andreas ;
Gebhard, Claudia ;
Strieder, Nicholas ;
Fischer, Alexander ;
Rehli, Michael ;
Hoffmann, Petra ;
Edinger, Matthias ;
Strowig, Till ;
Huehn, Jochen ;
Schmidl, Christian ;
Werner, Jens M. ;
Prantl, Lukas ;
Brors, Benedikt ;
Imbusch, Charles D. ;
Feuerer, Markus .
IMMUNITY, 2021, 54 (04) :702-+
[5]   Precursors for Nonlymphoid-Tissue Treg Cells Reside in Secondary Lymphoid Organs and Are Programmed by the Transcription Factor BATF [J].
Delacher, Michael ;
Imbusch, Charles D. ;
Hotz-Wagenblatt, Agnes ;
Mallm, Jan-Philipp ;
Bauer, Katharina ;
Simon, Malte ;
Riegel, Dania ;
Rendeiro, Andre F. ;
Bittner, Sebastian ;
Sanderink, Lieke ;
Pant, Asmita ;
Schmidleithner, Lisa ;
Braband, Kathrin L. ;
Echtenachter, Bernd ;
Fischer, Alexander ;
Giunchiglia, Valentina ;
Hoffmann, Petra ;
Edinger, Matthias ;
Bock, Christoph ;
Rehli, Michael ;
Brors, Benedikt ;
Schmidl, Christian ;
Feuerer, Markus .
IMMUNITY, 2020, 52 (02) :295-+
[6]   Th17 Cells Induce Colitis and Promote Th1 Cell Responses through IL-17 Induction of Innate IL-12 and IL-23 Production [J].
Feng, Ting ;
Qin, Hongwei ;
Wang, Lanfang ;
Benveniste, Etty N. ;
Elson, Charles O. ;
Cong, Yingzi .
JOURNAL OF IMMUNOLOGY, 2011, 186 (11) :6313-6318
[7]   MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data [J].
Finak, Greg ;
McDavid, Andrew ;
Yajima, Masanao ;
Deng, Jingyuan ;
Gersuk, Vivian ;
Shalek, Alex K. ;
Slichter, Chloe K. ;
Miller, Hannah W. ;
McElrath, M. Juliana ;
Prlic, Martin ;
Linsley, Peter S. ;
Gottardo, Raphael .
GENOME BIOLOGY, 2015, 16
[8]   The Key Role of Segmented Filamentous Bacteria in the Coordinated Maturation of Gut Helper T Cell Responses [J].
Gaboriau-Routhiau, Valerie ;
Rakotobe, Sabine ;
Lecuyer, Emelyne ;
Mulder, Imke ;
Lan, Annaig ;
Bridonneau, Chantal ;
Rochet, Violaine ;
Pisi, Annamaria ;
De Paepe, Marianne ;
Brandi, Giovanni ;
Eberl, Gerard ;
Snel, Johannes ;
Kelly, Denise ;
Cerf-Bensussan, Nadine .
IMMUNITY, 2009, 31 (04) :677-689
[9]   Shaping of Intestinal Microbiota in Nlrp6-and Rag2-Deficient Mice Depends on Community Structure [J].
Galvez, Eric J. C. ;
Iljazovic, Aida ;
Gronow, Achim ;
Flavell, Richard ;
Strowig, Till .
CELL REPORTS, 2017, 21 (13) :3914-3926
[10]   p53 Mediates TNF-Induced Epithelial Cell Apoptosis in IBD [J].
Goretsky, Tatiana ;
Dirisina, Ramanarao ;
Sinh, Preetika ;
Mittal, Navdha ;
Managlia, Elizabeth ;
Williams, David B. ;
Posca, Daniela ;
Ryu, Hyunji ;
Katzman, Rebecca B. ;
Barrett, Terrence A. .
AMERICAN JOURNAL OF PATHOLOGY, 2012, 181 (04) :1306-1315