Gender-specific expression of β1 integrin of VLA-4 in myelin basic protein-primed T cells: Implications for gender bias in multiple sclerosis

Saurav Brahmachari, Kalipada Pahan

Research output: Contribution to journalArticlepeer-review

Abstract

Susceptibility to multiple sclerosis is higher in females than males. However, the underlying mechanism behind this gender difference is poorly understood. Because the presence of neuroantigen-primed T cells in the CNS is necessary to initiate the neuroinflammatory cascade of multiple sclerosis, we first investigated how these T cells interacted with astroglia, major resident glial cells of the CNS. Interestingly, we found that myelin basic protein (MBP)-primed T cells from female and castrated male mice, but not from male mice, produced proinflammatory molecules, such as NO, IL-1β, and IL-6 in astroglia, and these responses were purely via contact between T cells and astroglia. Because T cell:glia contact requires several integrin molecules, we examined the involvement of integrins in this process. Both α4 and β1, subunits of VLA-4 integrin, were found to be necessary for T cell contact-induced generation of proinflammatory molecules in astroglia. Interestingly, the expression of β1, but not α4, was absent in male MBP-primed T cells. In contrast, female and castrated male MBP-primed T cells expressed both α4 and β1. Similarly, we also detected β1 in spleen of normal young female, but not male, mice. Furthermore, we show that male sex hormones (testosterone and dihydrotestosterone), but not female sex hormones (estrogen and progesterone), were able to suppress the mRNA expression of β1 in female MBP-primed T cells. These studies suggest that β1, but not α4, integrin of VLA-4 is the sex-specific molecule on T cell surface, and that the presence or absence of β1 determines gender-specific T cell contact-mediated glial activation.

Original languageEnglish (US)
Pages (from-to)6103-6113
Number of pages11
JournalJournal of Immunology
Volume184
Issue number11
DOIs
StatePublished - Jun 1 2010
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Gender-specific expression of β1 integrin of VLA-4 in myelin basic protein-primed T cells: Implications for gender bias in multiple sclerosis'. Together they form a unique fingerprint.

Cite this