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J Immunol ; 186(3): 1531-7, 2011 Feb 01.
Article in English | MEDLINE | ID: mdl-21178008

ABSTRACT

Retinoic acid-related orphan receptor (ROR)γt(+) TCRαß(+) 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.


Subject(s)
Cell Proliferation , Interleukin-17/biosynthesis , Intestinal Mucosa/immunology , Intestinal Mucosa/microbiology , Nuclear Receptor Subfamily 1, Group F, Member 3/deficiency , Receptors, Antigen, T-Cell/deficiency , T-Lymphocytes, Helper-Inducer/immunology , T-Lymphocytes, Helper-Inducer/microbiology , Amino Acid Sequence , Animals , CD4 Lymphocyte Count , Cell Differentiation/genetics , Cell Differentiation/immunology , 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 , Interleukin-17/genetics , Intestinal Mucosa/pathology , 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/genetics , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell/physiology , T-Lymphocytes, Helper-Inducer/pathology
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