期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 123, 期 5, 页码 977-983出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2009.03.030
关键词
Regulation of T effector cell lineage differentiation; T(H)17 cells; regulatory T cells; immune dysregulation; polyendocrinopathy; enteropathy; X-linked syndrome; forkhead box protein 3; autosomal dominant hyper-IgE syndrome; signal transducer and activator of transcription 3; IL-17; TGF-beta; IL-10
资金
- NIAID NIH HHS [R01 AI073542-03, R01 AI073542-01, R01 AI073542, R01 AI073542-02] Funding Source: Medline
- NICHD NIH HHS [R37 HD017427-43, R37 HD017427] Funding Source: Medline
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENT [R37HD017427] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI073542] Funding Source: NIH RePORTER
After activation by unique cytokines, CD4+ naive T cells differentiate into lineages of helper/effector (T-H) and regulatory T (Treg) cells that are characterized by distinct developmental pathways and unique biologic functions. The trusted binary system of T(H)1 and T(H)2 has been expanded to include the IL-17-producing T(H)17 cell lineage, which plays a role in immune responses to infectious agents and maintenance of autoimmune diseases. Acting as counterbalance, Treg cells maintain peripheral tolerance and protect the host from autoaggressive lymphocytes. T(H)1 cells produce IFN-gamma and are involved in cell-mediated immunity, T(H)2 cells produce IL-4 and contribute to Immoral immunity, T(H)17 cells generate IL-17 and play an important role in immune responses to fungi and extracellular pathogens, and forkhead box protein 3-positive (FOXP3(+)) Treg cells secrete TGF-beta and IL-10 and downregulate effector T cells. Autosomal dominant hyper-IgE syndrome, a rare primary immunodeficiency disorder, is caused by hypomorphic heterozygous mutations of signal transducer and activator of transcription 3 (STAT3), preventing T(H)17 lineage differentiation and increasing susceptibility to Staphylococcus and Candida species infections. Mutations in the FOXP3 gene interfere with Treg cell development and cause immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome. Other single-gene defects resulting in reduced Treg cell function include CD25, signal transducer and activator of transcription 51), autoimmune regulator, and Wiskott-Aldrich syndrome protein. These observations emphasize the importance of functionally distinct T-cell lineages in maintaining a balanced innate and cognate immune system. (J Allergy Clin Immunol 2009;123:977-83.)
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