TY - JOUR
T1 - Gender-specific expression of β1 integrin of VLA-4 in myelin basic protein-primed T cells
T2 - Implications for gender bias in multiple sclerosis
AU - Brahmachari, Saurav
AU - Pahan, Kalipada
PY - 2010/6/1
Y1 - 2010/6/1
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.0804356
DO - 10.4049/jimmunol.0804356
M3 - Article
C2 - 20483780
AN - SCOPUS:77953366081
SN - 0022-1767
VL - 184
SP - 6103
EP - 6113
JO - Journal of Immunology
JF - Journal of Immunology
IS - 11
ER -