Lu Ning, Li Ying, Zhang Zhiqiang, Xing Junji, Sun Ying, Yao Sheng, Chen Lieping
CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Department of Immunology and Center for Cancer Immunology Research, The University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030, USA.
Nat Commun. 2018 Feb 21;9(1):742. doi: 10.1038/s41467-018-03128-9.
Semaphorin-4A (Sema4A) has been implicated in the co-stimulation of T cells and drives Th1 immune responses by binding to the receptor T-cell immunoglobulin and mucin domain protein 2 (Tim-2) in mice. Here we show that human, but not murine, Sema4A is preferentially expressed on antigen-presenting cells, and co-stimulates CD4 T-cell proliferation and drives Th2 responses. By employing two independent cloning strategies, we demonstrate that Immunoglobulin-like transcript 4 (ILT-4) is a receptor for human SEMA4A (hSEMA4A) on activated CD4 T cells. We also find hSEMA4A to be highly expressed in human asthmatic lung tissue, implying its potential function in disease pathogenesis. Our study defines a different biological function of hSEMA4A from its murine homolog through its binding to the receptor of ILT-4 to co-stimulate CD4T cells and regulate Th2 cells differentiation.
信号素4A（Sema4A）与T细胞的共刺激有关，并通过与小鼠中的受体T细胞免疫球蛋白和粘蛋白结构域蛋白2（Tim-2）结合来驱动Th1免疫反应。在此我们表明，人源而非鼠源的Sema4A优先在抗原呈递细胞上表达，并共刺激CD4 T细胞增殖并驱动Th2反应。通过采用两种独立的克隆策略，我们证明免疫球蛋白样转录物4（ILT-4）是活化的CD4 T细胞上人类Sema4A（hSema4A）的受体。我们还发现hSema4A在人类哮喘肺组织中高度表达，这暗示了其在疾病发病机制中的潜在功能。我们的研究通过hSema4A与ILT-4受体结合以共刺激CD4 T细胞并调节Th2细胞分化，确定了hSema4A与其鼠源同系物不同的生物学功能。
