TH17 cells and regulatory T cells in primary immunodeficiency diseases

被引:104
作者
Ochs, Hans D. [1 ,2 ]
Oukka, Mohamed [3 ]
Torgerson, Troy R. [2 ]
机构
[1] Univ Washington, Seattle Childrens Hosp, Seattle Childrens Res Inst, Dept Pediat, Seattle, WA 98101 USA
[2] Univ Washington, Dept Pediat, Sch Med, Seattle, WA 98101 USA
[3] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Mol Immunol,Ctr Neurol Dis, Boston, MA 02115 USA
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; GROWTH-FACTOR-BETA; WISKOTT-ALDRICH-SYNDROME; HYPER-IGE SYNDROME; TGF-BETA; TH17; CELLS; SIGNAL TRANSDUCER; SYNDROME PROTEIN; STAT3; MUTATIONS; DIFFERENTIATION; CYTOKINE;
D O I
10.1016/j.jaci.2009.03.030
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
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.)
引用
收藏
页码:977 / 983
页数:7
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