期刊
HUMAN GENETICS
卷 139, 期 6-7, 页码 993-1000出版社
SPRINGER
DOI: 10.1007/s00439-020-02120-y
关键词
-
资金
- National Institute of Allergy and Infectious Diseases [5R37AI095983]
- Rockefeller University
- St. Giles Foundation
- National Institute of Health and Medical Research (INSERM)
- Foundation for Medical Research (FRM)
- French National Research Agency under the Investments for the future program [ANR-10-IAHU-01]
- ANR-GENMSMD [ANR-16-CE17-0005-01]
- SRC 2017
- ECOS Nord [C14S011, C19S01-63407]
- Paris University
- Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence [ANR-10-LABX-62-IBEID]
- Agence Nationale de la Recherche (ANR) [ANR-16-CE17-0005] Funding Source: Agence Nationale de la Recherche (ANR)
Mendelian susceptibility to mycobacterial disease (MSMD) is caused by inborn errors of IFN-gamma immunity. Affected patients are highly and selectively susceptible to weakly virulent mycobacteria, such as environmental mycobacteria and Bacillus Calmette-Guerin vaccines. Since 1996, disease-causing mutations have been reported in 15 genes, with allelic heterogeneity leading to 30 genetic disorders. Here, we briefly review the progress made in molecular, cellular, immunological, and clinical studies of MSMD since the last review published in 2018. Highlights include the discoveries of new genetic etiologies of MSMD: autosomal recessive (AR) complete deficiencies of (1) SPPL2a, (2) IL-12R beta 2, and (3) IL-23R, and (4) homozygosity for TYK2 P1104A, resulting in selective impairment of responses to IL-23. The penetrance of SPPL2a deficiency for MSMD is high, probably complete, whereas that of IL-12R beta 2 and IL-23R deficiencies, and TYK2 P1104A homozygosity, is incomplete, and probably low. SPPL2a deficiency has added weight to the notion that human cDC2 and Th1* cells are important for antimycobacterial immunity. Studies of IL-12R beta 2 and IL-23R deficiencies, and of homozygosity for P1104A TYK2, have shown that both IL-12 and IL-23 are required for optimal levels of IFN-gamma. These recent findings illustrate how forward genetic studies of MSMD are continuing to shed light on the mechanisms of protective immunity to mycobacteria in humans.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据