Human Semaphorin-4A drives Th2 responses by binding to receptor ILT-4

Ning Lu (), Ying Li, Zhiqiang Zhang, Junji Xing, Ying Sun, Sheng Yao and Lieping Chen
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Ning Lu: Chinese Academy of Sciences
Ying Li: Chinese Academy of Sciences
Zhiqiang Zhang: The University of Texas M.D. Anderson Cancer Center
Junji Xing: Texas Medical Center
Ying Sun: King’s College London
Sheng Yao: Yale University School of Medicine
Lieping Chen: Yale University School of Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-11

Abstract: Abstract 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 CD4+T cells and regulate Th2 cells differentiation.

Date: 2018
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DOI: 10.1038/s41467-018-03128-9

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