Precocious Interleukin 21 Expression in Naive Mice Identifies a Natural Helper Cell Population in Autoimmune Disease
| Autor: | Gregory J. Christianson, Gregory W. Carter, Thomas J. Sproule, Theodore Duffy, Giljun Park, Shweta Jain, Derry C. Roopenian, Herbert C. Morse, Xu-Long Wang, Hongsheng Wang, Sarah Kate Lane-Reticker, Elisabeth A. Marnik |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Mice Transgenic T-follicular helper cells Biology T-Lymphocytes Regulatory General Biochemistry Genetics and Molecular Biology Article K/BxN T-regulatory cells 03 medical and health sciences Interleukin 21 Mice 0302 clinical medicine IL-21 Nuclear Receptor Subfamily 4 Group A Member 1 Cytotoxic T cell Animals IL-2 receptor lcsh:QH301-705.5 Interleukin 3 B-Lymphocytes Arthritis Interleukins interleukin-21 autoimmunity FOXP3 Forkhead Transcription Factors T-Lymphocytes Helper-Inducer Natural killer T cell Autoimmune regulator Gastrointestinal Microbiome Immunity Humoral Mice Inbred C57BL 030104 developmental biology Gene Expression Regulation lcsh:Biology (General) Immunology Interleukin 12 030215 immunology Signal Transduction Transcription Factors |
| Zdroj: | Cell Reports, Vol 21, Iss 1, Pp 208-221 (2017) |
| ISSN: | 2211-1247 |
| Popis: | Summary Interleukin 21 (IL-21) plays key roles in humoral immunity and autoimmune diseases. It is known to function in mature CD4 + T follicular B cell helper (T FH ) cells, but its potential involvement in early T cell ontogeny is unclear. Here, we find that a significant population of newly activated thymic and peripheral CD4 + T cells functionally expresses IL-21 soon after birth. This naturally occurring population, termed natural (n)T H 21 cells, exhibits considerable similarity to mature T FH cells. nT H 21 cells originating and activated in the thymus are strictly dependent on autoimmune regulator (AIRE) and express high levels of NUR77, consistent with a bias toward self-reactivity. Their activation/expansion in the periphery requires gut microbiota and is held in check by FoxP3 + T REG cells. nT H 21 cells are the major thymic and peripheral populations of IL-21 + cells to expand in an IL-21-dependent humoral autoimmune disease. These studies link IL-21 to T cell ontogeny, self-reactivity, and humoral autoimmunity. |
| Databáze: | OpenAIRE |
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