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Biology subjects

Fettig, N. M.

Publications and source records attributed to Fettig, N. M..

2 recordsLinked to original sources

The dietary fiber guar gum ameliorates experimental autoimmune encephalomyelitis via attenuated Th1 activation and differentiation

Dietary fibers are potent modulators of immune responses that can restrain inflammation in multiple disease contexts. However, dietary fibers encompass a biochemically diverse family of carbohydrates, and it remains unknown how different fiber sources influence immunity. In a head-to-head comparison of four different high-fiber diets, we demonstrate a unique and potent ability of guar gum to reduce neuroinflammation in experimental autoimmune encephalomyelitis (EAE), a T cell-mediated mouse model of multiple sclerosis. CD4+ T cells from guar gum-fed mice have blunted Th1-skewing, reduced migratory capacity, and limited activation and proliferative capabilities. These changes are not explained by guar gum-specific alterations to the microbiota at the 16S rRNA level, nor by specific alterations in short chain fatty acids. These findings demonstrate specificity in the host response to fiber sources, and define a new pathway of fiber-induced CD4+ T cell immunomodulation that protects against pathologic neuroinflammation.

immunology↗

Epstein-Barr virus infection promotes Th1-mediated disease in a humanized immune mouse model of multiple sclerosis

Infection with the human-tropic Epstein-Barr virus (EBV) is a strong risk factor for multiple sclerosis (MS), though the underlying mechanisms remain unclear. To investigate the immunomodulatory effects of latent EBV infection, we induced experimental autoimmune encephalomyelitis (EAE) in immunocompromised mice humanized with peripheral blood mononuclear cells (PBMCs) from individuals with or without a history of EBV infection and/or a diagnosis of relapsing MS. HuPBMC EAE mice generated from EBV seronegative healthy donors were less susceptible to developing severe clinical disease than EBV seropositive healthy donor and RRMS cohorts. Donor EBV seropositivity and RRMS led to a significant incremental increase in the number of brain and spinal cord infiltrating effector T cells, in the absence of viral reactivation, due to enhanced proliferation of donor T cells and reduced regulatory T cell expansion. The data indicate that a history of EBV infection, further compounded by a diagnosis of RRMS, promotes T cell-mediated disease in a novel humanized mouse model of MS. SUMMARYIn a novel humanized mouse model of multiple sclerosis (MS), donor history of Epstein-Barr virus (EBV) infection exacerbates disease severity by skewing the balance of effector and regulatory T cells in the brain and spinal cord. These results reveal an immunomodulatory mechanism by which latent EBV infection could predispose to the development of autoimmune disease.

immunology↗