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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| Veröffentlicht in: | The Journal of immunology (1950) 2011-02, Vol.186 (3), p.1531-1537 |
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| container_title | The Journal of immunology (1950) |
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| creator | Lochner, Matthias Bérard, Marion Sawa, Shinichiro Hauer, Siona Gaboriau-Routhiau, Valérie Fernandez, Tahia Diana Snel, Johannes Bousso, Philippe Cerf-Bensussan, Nadine Eberl, Gérard |
| description | 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. |
| doi_str_mv | 10.4049/jimmunol.1001723 |
| format | Article |
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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.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.1001723</identifier><identifier>PMID: 21178008</identifier><language>eng</language><publisher>United States: Publisher : Baltimore : Williams & Wilkins, c1950-. 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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.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>CD4 Lymphocyte Count</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Differentiation - immunology</subject><subject>Cell Proliferation</subject><subject>Female</subject><subject>Forkhead Transcription Factors - biosynthesis</subject><subject>Forkhead Transcription Factors - deficiency</subject><subject>Forkhead Transcription Factors - genetics</subject><subject>Germ-Free Life - genetics</subject><subject>Germ-Free Life - immunology</subject><subject>Gram-Positive Bacterial Infections - immunology</subject><subject>Gram-Positive Bacterial Infections - pathology</subject><subject>Green Fluorescent Proteins - biosynthesis</subject><subject>Green Fluorescent Proteins - genetics</subject><subject>Immunology</subject><subject>Interleukin-17 - biosynthesis</subject><subject>Interleukin-17 - genetics</subject><subject>Intestinal Mucosa - immunology</subject><subject>Intestinal Mucosa - microbiology</subject><subject>Intestinal Mucosa - pathology</subject><subject>Life Sciences</subject><subject>Lymphocyte Activation - genetics</subject><subject>Lymphocyte Activation - immunology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Mice, Transgenic</subject><subject>Molecular Sequence Data</subject><subject>Nuclear Receptor Subfamily 1, Group F, Member 3 - biosynthesis</subject><subject>Nuclear Receptor Subfamily 1, Group F, Member 3 - deficiency</subject><subject>Nuclear Receptor Subfamily 1, Group F, Member 3 - genetics</subject><subject>Receptors, Antigen, T-Cell - deficiency</subject><subject>Receptors, Antigen, T-Cell - genetics</subject><subject>Receptors, Antigen, T-Cell - physiology</subject><subject>T-Lymphocytes, Helper-Inducer - immunology</subject><subject>T-Lymphocytes, Helper-Inducer - microbiology</subject><subject>T-Lymphocytes, Helper-Inducer - pathology</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1r3DAQxUVpaTYf956Kbj05Hdn6PIalbQILgbA9i7E1m1Wwra1lF_rfV8tucs1pYOb3Zh7zGPsi4FaCdN9f4jAsY-pvBYAwdfOBrYRSUGkN-iNbAdR1JYw2F-wy5xcA0FDLz-yiFsJYALti-yfK8xS7mQIfYjelNqYZOY6BY5tp7IinHe_S84gz8e36qYzm-Ewj7wlD5nMqDb6MLfZY4MDLiCacYxqPwu1eGN5R3-dr9mmHfaabc71iv3_-2K7vq83jr4f13abqpNFz1UEbwIiGnHaq-EfdOYuyqXfShBbrFkkGaZV1DoxrLQpBwoFSpJQNKjRXrDrt3WPvD1MccPrnE0Z_f7fxB8wzLZMHUFpqLf-Kwn878Ycp_VnKM_wQ89ExjpSW7MsZoYTT75NW6uLKaFtIOJHlnzlPtHszIsAfg_OvwflzcEXy9bx8aQcKb4LXpJr_V9yUog</recordid><startdate>20110201</startdate><enddate>20110201</enddate><creator>Lochner, Matthias</creator><creator>Bérard, Marion</creator><creator>Sawa, Shinichiro</creator><creator>Hauer, Siona</creator><creator>Gaboriau-Routhiau, Valérie</creator><creator>Fernandez, Tahia Diana</creator><creator>Snel, Johannes</creator><creator>Bousso, Philippe</creator><creator>Cerf-Bensussan, Nadine</creator><creator>Eberl, Gérard</creator><general>Publisher : Baltimore : Williams & Wilkins, c1950-. 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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.</abstract><cop>United States</cop><pub>Publisher : Baltimore : Williams & Wilkins, c1950-. 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| 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 |
| title | Restricted microbiota and absence of cognate TCR antigen leads to an unbalanced generation of Th17 cells |
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