Abstract
IL-17A and IL-17F regulate granulopoiesis and are produced by memory T cells. Rag1(-/-) recombinase-activating gene-deficient mice cannot produce mature T cells but maintain normal neutrophil counts. Athymic nude mice are neutropenic or have near-normal neutrophil counts, depending on the prevailing intestinal flora, and do not produce IL-17A. By contrast, thymi from Rag1(-/-) mice contain as much IL-17A as those from wild-type (WT) mice. IL-17A-producing cells are found in the double negative DN1 compartment of the Rag1(-/-) thymus and express intracellular CD3. These cells colonize the spleen and mesenteric lymph node and secrete IL-17A in vitro following stimulation with IL-23 at a level similar to that of WT splenocytes. Adoptively transferred Rag1(-/-) or WT thymocytes correct neutrophil counts in neutropenic nude mice. We conclude that the development of IL-17A-producing T-lineage cells requires an intact thymic epithelium, but not V(D)J recombination.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibody Diversity / genetics
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Cell Lineage / genetics
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Cell Lineage / immunology
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Epithelium / immunology
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Epithelium / metabolism
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Gene Rearrangement, T-Lymphocyte* / immunology
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Immunoglobulin Heavy Chains / genetics
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Immunoglobulin Heavy Chains / metabolism
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Immunoglobulin Joining Region / genetics
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Immunoglobulin Joining Region / metabolism
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Immunoglobulin Variable Region / genetics
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Immunoglobulin Variable Region / metabolism
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Interleukin-17 / biosynthesis*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Nude
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Mice, Transgenic
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Neutropenia / genetics
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Neutropenia / immunology
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Neutropenia / metabolism
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Neutrophils / immunology*
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Neutrophils / metabolism*
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Neutrophils / pathology
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Receptors, Antigen, T-Cell / genetics*
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Receptors, Antigen, T-Cell / metabolism
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism
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T-Lymphocyte Subsets / transplantation
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Thymus Gland / cytology*
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Thymus Gland / immunology*
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Thymus Gland / metabolism
Substances
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Il17a protein, mouse
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Immunoglobulin Heavy Chains
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Immunoglobulin Joining Region
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Immunoglobulin Variable Region
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Interleukin-17
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Receptors, Antigen, T-Cell