Restricted microbiota and absence of cognate TCR antigen leads to an unbalanced generation of Th17 cells

Retinoic acid-related orphan receptor (ROR)γt(+) TCRαβ(+) cells expressing IL-17, termed Th17 cells, are most abundant in the intestinal lamina propria. Symbiotic microbiota are required for the generation of Th17 cells, but the requirement for microbiota-derived Ag is not documented. In this study,...

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Bibliographic Details
Published in:	The Journal of immunology (1950) Vol. 186; no. 3; pp. 1531 - 1537
Main Authors:	Lochner, Matthias, Bérard, Marion, Sawa, Shinichiro, Hauer, Siona, Gaboriau-Routhiau, Valérie, Fernandez, Tahia Diana, Snel, Johannes, Bousso, Philippe, Cerf-Bensussan, Nadine, Eberl, Gérard
Format:	Journal Article
Language:	English
Published:	United States Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists 01-02-2011
Subjects:	Amino Acid Sequence Animals CD4 Lymphocyte Count Cell Differentiation - genetics Cell Differentiation - immunology Cell Proliferation Female Forkhead Transcription Factors - biosynthesis Forkhead Transcription Factors - deficiency Forkhead Transcription Factors - genetics Germ-Free Life - genetics Germ-Free Life - immunology Gram-Positive Bacterial Infections - immunology Gram-Positive Bacterial Infections - pathology Green Fluorescent Proteins - biosynthesis Green Fluorescent Proteins - genetics Immunology Interleukin-17 - biosynthesis Interleukin-17 - genetics Intestinal Mucosa - immunology Intestinal Mucosa - microbiology Intestinal Mucosa - pathology Life Sciences Lymphocyte Activation - genetics Lymphocyte Activation - immunology Male Mice Mice, Knockout Mice, Transgenic Molecular Sequence Data Nuclear Receptor Subfamily 1, Group F, Member 3 - biosynthesis Nuclear Receptor Subfamily 1, Group F, Member 3 - deficiency Nuclear Receptor Subfamily 1, Group F, Member 3 - genetics Receptors, Antigen, T-Cell - deficiency Receptors, Antigen, T-Cell - genetics Receptors, Antigen, T-Cell - physiology T-Lymphocytes, Helper-Inducer - immunology T-Lymphocytes, Helper-Inducer - microbiology T-Lymphocytes, Helper-Inducer - pathology LINEAGE COMMITMENT ADAPTIVE IMMUNITY RETINOIC ACID ROR-GAMMA-T HELPER-CELLS REGULATORY T-CELLS INTESTINAL IMMUNE-RESPONSES PROINFLAMMATORY IL-17(+) NKP46(+) CELLS FILAMENTOUS BACTERIA
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Summary:	Retinoic acid-related orphan receptor (ROR)γt(+) TCRαβ(+) cells expressing IL-17, termed Th17 cells, are most abundant in the intestinal lamina propria. Symbiotic microbiota are required for the generation of Th17 cells, but the requirement for microbiota-derived Ag is not documented. In this study, we show that normal numbers of Th17 cells develop in the intestine of mice that express a single TCR in the absence of cognate Ag, whereas the microbiota remains essential for their development. However, such mice, or mice monocolonized with the Th17-inducing segmented filamentous bacteria, fail to induce normal numbers of Foxp3(+) RORγt(+) T cells, the regulatory counterpart of IL-17(+)RORγt(+) T cells. These results demonstrate that a complex microbiota and cognate Ag are required to generate a properly regulated set of RORγt(+) T cells and Th17 cells.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	0022-1767 1550-6606
DOI:	10.4049/jimmunol.1001723