Publication Date:
2015-03-21
Description:
Aire is an important regulator of immunological tolerance, operating in a minute subset of thymic stromal cells to induce transcripts encoding peptides that guide T cell selection. Expression of Aire during a perinatal age window is necessary and sufficient to prevent the multiorgan autoimmunity characteristic of Aire-deficient mice. We report that Aire promotes the perinatal generation of a distinct compartment of Foxp3(+)CD4(+) regulatory T (Treg) cells, which stably persists in adult mice. This population has a role in maintaining self-tolerance, a transcriptome and an activation profile distinguishable from those of Tregs produced in adults. Underlying the distinct Treg populations are age-dependent, Aire-independent differences in the processing and presentation of thymic stromal-cell peptides, resulting in different T cell receptor repertoires. Our findings expand the notion of a developmentally layered immune system.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710357/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710357/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Siyoung -- Fujikado, Noriyuki -- Kolodin, Dmitriy -- Benoist, Christophe -- Mathis, Diane -- R01 DK060027/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2015 May 1;348(6234):589-94. doi: 10.1126/science.aaa7017. Epub 2015 Mar 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. Aging Intervention Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, 305-806, South Korea. ; Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. ; Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston MA 02115, USA. cbdm@hms.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25791085" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antigens, CD4/analysis
;
Autoimmunity
;
Forkhead Transcription Factors/analysis
;
Mice
;
Mice, Knockout
;
Receptors, Antigen, T-Cell/immunology
;
Self Tolerance/*genetics
;
T-Lymphocytes, Regulatory/*immunology
;
Transcription Factors/genetics/*physiology
;
Transcriptome
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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