Advertisement

 

 

CBirTox is a selective antigen-specific agonist of the Treg-IgA-microbiota homeostatic pathway.

CBirTox is a selective antigen-specific agonist of the Treg-IgA-microbiota homeostatic pathway.
Author Information (click to view)

Alexander KL, Katz J, Elson CO,


Alexander KL, Katz J, Elson CO, (click to view)

Alexander KL, Katz J, Elson CO,

Advertisement
Share on FacebookTweet about this on TwitterShare on LinkedIn

PloS one 2017 07 2712(7) e0181866 doi 10.1371/journal.pone.0181866
Abstract

Cultivating an environment of mutualism between host cells and the microbiota is vital, and dysregulation of this relationship is associated with multiple immune disorders including metabolic and skin diseases, asthma, allergy, and Inflammatory Bowel Disease (IBD). One prominent mechanism for maintaining homeostasis is the protective regulatory T cell (Treg)- Immunoglobulin A (IgA) pathway toward microbiota antigens, in which Tregs maintain homeostasis and provide critical survival factors to IgA+ B cells. In order to amplify the Treg-IgA pathway, we have generated a fusion protein, CBirTox, comprised of a portion of the carboxy terminus of CBir1, a microbiota flagellin, genetically coupled to Cholera Toxin B subunit (CTB) via the A2 linker of CT. Both dendritic cells (DCs) and B cells pulsed with CBirTox selectively induced functional CD4+Foxp3+ Tregs in vitro, and CBirTox augmented CD4+Foxp3+ cell numbers in vivo. The induced Foxp3 expression was independent of retinoic acid (RA) signaling but was inhibited by neutralization of TGF-β. CBirTox treatment of B cells downregulated mammalian target of rapamycin (mTOR) signaling. Furthermore, CBirTox-pulsed DCs induced substantial production of IgA from naïve B cells. Collectively these data demonstrate that CBirTox represents a novel approach to bolstering the Treg-IgA pathway at the host-microbiota interface.

Submit a Comment

Your email address will not be published. Required fields are marked *

16 − 14 =

[ HIDE/SHOW ]