CD4+ Group 1 Innate Lymphoid Cells (ILC) Form a Functionally Distinct ILC Subset That Is Increased in Systemic Sclerosis.
CD4+ Group 1 Innate Lymphoid Cells (ILC) Form a Functionally Distinct ILC Subset That Is Increased in Systemic Sclerosis.
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DOI：
10.4049/jimmunol.1501491
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发表时间：
2016-03-01
期刊：
影响因子：
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通讯作者：
Ziegler SF
中科院分区：
文献类型：
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作者：
Roan F;Stoklasek TA;Whalen E;Molitor JA;Bluestone JA;Buckner JH;Ziegler SF
先天性淋巴样细胞（inate lymphoid cells，ILC）是一组异质性的细胞亚群，在无抗原存在的情况下对先天性刺激产生大量的T细胞相关细胞因子。在这项研究中，我们定义了不同的模式，表面标志物和细胞因子表达的ILC的子集，可以进一步描绘他们的迁移和功能。最值得注意的是，我们发现先前定义为ILC 1的子集包含CD 4 + CD 8 −、CD 4 − CD 8+和CD 4 − CD 8 −群体。尽管所有ILC 1亚群与Th 1细胞具有共同特征，但CD 4 + ILC 1也表现出显著的表型和功能异质性。我们还发现，在系统性硬化症（SSc）患者的外周血中，CD 4 + ILC 1和NKp 44 + ILC 3的频率增加，而CD 4 − ILC 1或ILC 2则没有增加，SSc是一种以纤维化和血管病理以及免疫失调为特征的疾病。此外，我们证明了CD 4+和CD 4 − ILC 1在IL-6 R α表达的基础上在功能上是不同的，并且在SSc中IL-6 R α在ILC上的表达频率发生了改变。CD 4+和CD 4-ILC 1不同的表型和功能特征表明它们可能在系统性硬化症等免疫介导疾病的发病机制中发挥不同的作用。
Innate lymphoid cells (ILC) are a heterogeneous group of cellular subsets that produce large amounts of T cell-associated cytokines in response to innate stimulation in the absence of antigen. In this study, we define distinct patterns of surface marker and cytokine expression among the ILC subsets that may further delineate their migration and function. Most notably, we found that the subset previously defined as ILC1 contains CD4+ CD8−, CD4− CD8+ and CD4− CD8− populations. Although all ILC1 subsets shared characteristics with Th1 cells, CD4+ ILC1 also demonstrated significant phenotypic and functional heterogeneity. We also show that the frequencies of CD4+ ILC1 and NKp44+ ILC3, but not CD4− ILC1 or ILC2, are increased in the peripheral blood of individuals with systemic sclerosis (SSc), a disease characterized by fibrotic and vascular pathology as well as immune dysregulation. Furthermore, we demonstrate that CD4+ and CD4− ILC1 are functionally divergent based on their IL-6Rα expression, and that the frequency of IL-6Rα expression on ILC is altered in SSc. The distinct phenotypic and functional features of CD4+ and CD4− ILC1 suggest that they may have differing roles in the pathogenesis of immune-mediated diseases such as systemic sclerosis.