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.
Highlights
Th1 immune responses by binding to the receptor T-cell immunoglobulin and mucin domain protein 2 (Tim-2) in mice
To investigate the function of Sema4A in humans, we first detected the expression of Sema4A in various populations of human monocytes, dendritic cells (DCs), T cells, granulocytes, as well as B cells, NK cells, mast cells sorted from human peripheral blood mononuclear cells (PBMC) by using microarray gene expression analysis
Using quantitative PCR (Q-PCR) detection, we directly confirmed that Sema4A was most highly expressed in myeloid dendritic cells (mDCs), followed by B
Summary
Th1 immune responses by binding to the receptor T-cell immunoglobulin and mucin domain protein 2 (Tim-2) in mice. 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. 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. Semaphorins have been implicated in axon outgrowth, angiogenesis, bone differentiation, cardiovascular development, and regulation of immune responses[3,4,5]. Sema4A is not expressed by resting T cells. Sema4A is preferentially expressed by dendritic cells (DCs).
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