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

Area of Science:

• Immunology
• Cell Biology
• Molecular Biology

Background:

• Semaphorin-4A (Sema4A) is known to co-stimulate T cells and promote Th1 immune responses in mice via the T-cell immunoglobulin and mucin domain protein 2 (Tim-2) receptor.
• The specific role and receptor interactions of human Sema4A (hSEMA4A) in T-cell responses remain less understood.

Purpose of the Study:

• To investigate the function of human Sema4A (hSEMA4A) in T-cell co-stimulation and immune responses.
• To identify the specific receptor for hSEMA4A on human T cells.
• To explore the potential role of hSEMA4A in human diseases like asthma.

Main Methods:

• Comparative analysis of Sema4A expression and function in human versus murine systems.
• Utilized two independent cloning strategies to identify the hSEMA4A receptor.
• Assessed hSEMA4A expression in human asthmatic lung tissue.

Main Results:

• Human Sema4A (hSEMA4A) is preferentially expressed on antigen-presenting cells and co-stimulates CD4+ T-cell proliferation, driving Th2 responses.
• Immunoglobulin-like transcript 4 (ILT-4) was identified as the specific receptor for hSEMA4A on activated human CD4+ T cells.
• Elevated hSEMA4A expression was observed in human asthmatic lung tissue.

Conclusions:

• Human Sema4A (hSEMA4A) exhibits distinct biological functions compared to its murine homologue.
• The hSEMA4A-ILT-4 interaction plays a crucial role in co-stimulating human CD4+ T cells and regulating Th2 cell differentiation.
• hSEMA4A may be involved in the pathogenesis of human asthma.