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Human Semaphorin-4A drives Th2 responses by binding to receptor ILT-4
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Human Semaphorin-4A drives Th2 responses by binding to receptor ILT-4
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Journal Article
Human Semaphorin-4A drives Th2 responses by binding to receptor ILT-4
2018
Overview
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.
Semaphorin-4A is a cell surface protein with known functions in neural development and immune regulation, but the mechanism for immune modulation is unclear. Here the authors show that ILT-4, previously found on myeloid cells, is the receptor of Semaphorin-4A on activate human CD4 T cells for mediating T cell co-stimulation.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/31
/ 13/51
/ 14/19
/ 38/61
/ Animals
/ Antigen-Presenting Cells - cytology
/ Asthma
/ Binding
/ CD4-Positive T-Lymphocytes - cytology
/ Cloning
/ Homology
/ Humanities and Social Sciences
/ Humans
/ Lungs
/ Mice
/ Mucin
/ Oligonucleotide Array Sequence Analysis
/ Receptors, Antigen, T-Cell - metabolism
/ Receptors, Immunologic - physiology
/ Science
