PMID- 28750075
OWN - NLM
STAT- MEDLINE
DCOM- 20171009
LR  - 20211204
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 7
DP  - 2017
TI  - CBirTox is a selective antigen-specific agonist of the Treg-IgA-microbiota 
      homeostatic pathway.
PG  - e0181866
LID - 10.1371/journal.pone.0181866 [doi]
LID - e0181866
AB  - 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-beta. CBirTox treatment of B cells 
      downregulated mammalian target of rapamycin (mTOR) signaling. Furthermore, 
      CBirTox-pulsed DCs induced substantial production of IgA from naive B cells. 
      Collectively these data demonstrate that CBirTox represents a novel approach to 
      bolstering the Treg-IgA pathway at the host-microbiota interface.
FAU - Alexander, Katie L
AU  - Alexander KL
AD  - Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 
      United States of America.
FAU - Katz, Jannet
AU  - Katz J
AD  - Department of Pediatric Dentistry, University of Alabama at Birmingham, 
      Birmingham, AL, United States of America.
FAU - Elson, Charles O
AU  - Elson CO
AUID- ORCID: 0000-0001-8873-1534
AD  - Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 
      United States of America.
AD  - Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, 
      United States of America.
LA  - eng
GR  - P01 DK071176/DK/NIDDK NIH HHS/United States
PT  - Journal Article
DEP - 20170727
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (CBir1 flagellin)
RN  - 0 (Epitopes)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Foxp3 protein, mouse)
RN  - 0 (Immunoglobulin A)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Transforming Growth Factor beta)
RN  - 12777-81-0 (Flagellin)
RN  - 5688UTC01R (Tretinoin)
RN  - 9012-63-9 (Cholera Toxin)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Antigen-Presenting Cells/metabolism
MH  - B-Lymphocytes/immunology
MH  - Cell Line
MH  - Cholera Toxin/metabolism
MH  - Dendritic Cells/immunology
MH  - Epitopes/*immunology
MH  - Flagellin/*agonists
MH  - Forkhead Transcription Factors/metabolism
MH  - Genomics
MH  - *Homeostasis
MH  - Immunoglobulin A/*immunology
MH  - Intestines
MH  - Mice, Inbred C57BL
MH  - *Microbiota
MH  - Recombinant Fusion Proteins/metabolism
MH  - Signal Transduction
MH  - T-Lymphocytes, Regulatory/*immunology
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Transforming Growth Factor beta/metabolism
MH  - Tretinoin/metabolism
PMC - PMC5531474
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2017/07/28 06:00
MHDA- 2017/10/11 06:00
PMCR- 2017/07/27
CRDT- 2017/07/28 06:00
PHST- 2017/03/01 00:00 [received]
PHST- 2017/07/07 00:00 [accepted]
PHST- 2017/07/28 06:00 [entrez]
PHST- 2017/07/28 06:00 [pubmed]
PHST- 2017/10/11 06:00 [medline]
PHST- 2017/07/27 00:00 [pmc-release]
AID - PONE-D-17-08245 [pii]
AID - 10.1371/journal.pone.0181866 [doi]
PST - epublish
SO  - PLoS One. 2017 Jul 27;12(7):e0181866. doi: 10.1371/journal.pone.0181866. 
      eCollection 2017.