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Wang, E. J.

Publications and source records attributed to Wang, E. J..

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↗

Phosphosite T674A mutation in kinesin family member 3A fails to reproduce tissue and ciliary defects characteristic of CILK1 loss of function

Background Kinesin family member 3A (KIF3A) is a molecular motor protein in the heterotrimeric kinesin-2 complex that drives anterograde intraflagellar transport. This process plays a pivotal role in both biogenesis and maintenance of the primary cilium that supports tissue development. Ciliogenesis associated kinase 1 (CILK1) phosphorylates human KIF3A at Thr672. CILK1 loss of function causes ciliopathies that manifest profound and multiplex developmental defects, including polydactyly, shortened and hypoplastic bones and alveoli airspace deficiency, leading to perinatal lethality. Prior studies have raised the hypothesis that CILK1 phosphorylation of KIF3A is critical for its regulation of organ development.Results We produced a mouse model with phosphorylation site Thr674 in mouse Kif3a mutated to Ala. Kif3a T674A homozygotes are viable and exhibit no skeletal abnormalities, and only mildly reduced airspace in alveoli. Mouse embryonic fibroblasts carrying Kif3a T674A mutation show a normal rate of ciliation and a moderate increase in cilia length.Conclusion These results indicate that eliminating Kif3a Thr674 phosphorylation by CILK1 is insufficient to reproduce the severe developmental defects in ciliopathies caused by Cilk1 loss of function. This suggests KIF3A phosphorylation by CILK1 is not essential for tissue development and other substrates are involved in Cilk1 ciliopathies.Competing Interest StatementThe authors have declared no competing interest.View Full Text

developmental biology↗