Cutting edge: Type I IFN reverses human Th2 commitment and stability by suppressing GATA3.
Cutting edge: Type I IFN reverses human Th2 commitment and stability by suppressing GATA3.
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DOI：
10.4049/jimmunol.1000469
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发表时间：
2010-07-15
期刊：
影响因子：
--
通讯作者：
Farrar JD
中科院分区：
文献类型：
--
作者：
Huber JP;Ramos HJ;Gill MA;Farrar JD
Th 2细胞调节蠕虫感染的炎症反应，同时也介导哮喘和过敏的病理过程。IL-4通过诱导GATA 3转录因子的表达促进Th 2发育，并且Th 2表型通过GATA 3依赖性自身调节环稳定。在本研究中，我们发现I型干扰素（IFN-α/β）阻断人Th 2发育并抑制定型Th 2细胞分泌细胞因子。这种负调节途径在人而不是小鼠CD 4 + T细胞中起作用，并且对I型干扰素具有选择性，因为IFN-γ和IL-12都不介导这种抑制。IFN-α/β通过在Th 2发育期间和完全定型的Th 2细胞中抑制GATA 3来阻断Th 2细胞因子分泌。通过逆转录病毒异位表达GATA 3不能克服IFN-α/β介导的Th 2定型抑制。因此，我们证明了IFN-α/β在阻断Th 2细胞中的新作用，表明其作为特应性和哮喘的有希望的治疗的潜力。
Th2 cells regulate inflammatory responses to helminth infections while also mediating pathological processes of asthma and allergy. IL-4 promotes Th2 development by inducing the expression of the GATA3 transcription factor, and the Th2 phenotype is stabilized by a GATA3-dependent auto-regulatory loop. In this study, we found that type I interferon (IFN-α/β) blocked human Th2 development and inhibited cytokine secretion from committed Th2 cells. This negative regulatory pathway was operative in human but not mouse CD4+ T cells and was selective to type I interferon as neither IFN-γ nor IL-12 mediated such inhibition. IFN-α/β blocked Th2 cytokine secretion through the inhibition of GATA3 during Th2 development and in fully committed Th2 cells. Ectopic expression of GATA3 via retrovirus did not overcome IFN-α/β-mediated inhibition of Th2 commitment. Thus, we demonstrate a novel role for IFN-α/β in blocking Th2 cells, suggesting its potential as a promising therapy for atopy and asthma.
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DOI：
10.4049/jimmunol.181.12.8204
发表时间：
2008-12-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Davis AM;Ramos HJ;Davis LS;Farrar JD
通讯作者：
Farrar JD
DOI：
10.1111/j.1365-2222.2009.03241.x
发表时间：
2009-06
期刊：
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
影响因子：
--
作者：
Wang YH;Liu YJ
通讯作者：
Liu YJ
影响因子：
32.4
作者：
Hegazy, Ahmed N.;Peine, Michael;Loehning, Max
通讯作者：
Loehning, Max
影响因子：
15.9
作者：
Schandene, L;DelPrete, GF;Goldman, M
通讯作者：
Goldman, M
影响因子：
4.4
作者：
Pene, Jerome;Chevalier, Sylvie;Gascan, Hugues
通讯作者：
Gascan, Hugues