PMID- 30085016
OWN - NLM
STAT- MEDLINE
DCOM- 20190320
LR  - 20220330
IS  - 1876-4479 (Electronic)
IS  - 1873-9946 (Print)
IS  - 1873-9946 (Linking)
VI  - 12
IP  - 12
DP  - 2018 Nov 28
TI  - C/EBPbeta Deletion Promotes Expansion of Poorly Functional Intestinal Regulatory T 
      Cells.
PG  - 1475-1485
LID - 10.1093/ecco-jcc/jjy105 [doi]
AB  - BACKGROUND AND AIMS: Inflammatory Bowel Diseases [IBDs] are chronic intestinal 
      inflammatory conditions in part mediated by CD4+ T cells. Anti-inflammatory 
      Foxp3+ regulatory T cells [Tregs] maintain immune homeostasis and protect against 
      IBD development via multiple mechanisms, including cytokine secretion and 
      cell-cell interaction. CCAAT enhancer binding protein-beta [C/EBPbeta] is a 
      stress-responsive transcription factor linked with IBD susceptibility. Whole-body 
      C/EBPbeta deficiency induces CD4+ T cell-predominant hyperproliferation, and we 
      hypothesize that this may be due to impaired Treg function. METHODS: We used the 
      C/EBPbeta-/- mice in the CD45RBHigh adoptive transfer model, to assess C/EBPbeta-/- 
      CD4+ T cells for their colitiogenic potential, and C/EBPbeta-/- CD4+ Foxp3+ Tregs 
      for their ability to inhibit colitis. We assessed Tregs from the C/EBPbeta-/- mice 
      for expression of Treg functional genes and proteins. RESULTS: Naive C/EBPbeta-/- 
      CD4+ T cells are more colitogenic in vivo. The exacerbated colitis does not 
      appear to reflect impaired Treg development, however, as C/EBPbeta-/- mice displayed 
      more, rather than fewer intestinal CD4+Foxp3+ Tregs in vivo. Instead, this 
      reflects impaired Treg function as seen by the reduced capacity to suppress T 
      cell proliferation in vitro, along with decreased secretion of the 
      anti-inflammatory cytokine IL-10. These findings were corroborated in vivo by 
      additional adoptive co-transfer studies in which wildtype Tregs prevented colitis 
      but C/EBPbeta-/- Tregs did not. CONCLUSION: C/EBPbeta deficiency impairs Treg function 
      and potentiates T cell-mediated colitis. A clearer understanding of the function 
      of this transcription factor may provide a novel therapeutic strategy for IBD.
FAU - Collins, Colm B
AU  - Collins CB
AD  - Section of Pediatric Gastroenterology, Hepatology and Nutrition, Digestive Health 
      Institute, Children's Hospital Colorado, Aurora, CO, USA.
AD  - Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, 
      USA.
AD  - Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, 
      CO, USA.
FAU - Puthoor, Pamela R
AU  - Puthoor PR
AD  - Section of Pediatric Gastroenterology, Hepatology and Nutrition, Digestive Health 
      Institute, Children's Hospital Colorado, Aurora, CO, USA.
AD  - Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, 
      USA.
AD  - Pediatric Inflammatory Bowel Disease Center, Children's Hospital Colorado, 
      Aurora, CO, USA.
FAU - Nguyen, Tom T
AU  - Nguyen TT
AD  - Section of Pediatric Gastroenterology, Hepatology and Nutrition, Digestive Health 
      Institute, Children's Hospital Colorado, Aurora, CO, USA.
AD  - Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, 
      USA.
AD  - Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, 
      CO, USA.
FAU - Strassheim, Derek
AU  - Strassheim D
AD  - Department of Medicine, University of Colorado, Aurora, CO, USA.
FAU - Jedlicka, Paul
AU  - Jedlicka P
AD  - Department of Pathology, University of Colorado School of Medicine, Aurora, CO, 
      USA.
FAU - Friedman, Jacob E
AU  - Friedman JE
AD  - Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, 
      USA.
FAU - de Zoeten, Edwin F
AU  - de Zoeten EF
AD  - Section of Pediatric Gastroenterology, Hepatology and Nutrition, Digestive Health 
      Institute, Children's Hospital Colorado, Aurora, CO, USA.
AD  - Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, 
      USA.
AD  - Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, 
      CO, USA.
AD  - Pediatric Inflammatory Bowel Disease Center, Children's Hospital Colorado, 
      Aurora, CO, USA.
LA  - eng
GR  - K08 DK080189/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PL  - England
TA  - J Crohns Colitis
JT  - Journal of Crohn's & colitis
JID - 101318676
RN  - 0 (CCAAT-Enhancer-Binding Protein-beta)
RN  - 0 (Cytokines)
SB  - IM
EIN - J Crohns Colitis. 2019 Apr 26;13(5):672. PMID: 30624617
MH  - Animals
MH  - CCAAT-Enhancer-Binding Protein-beta/*metabolism
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - *Colitis/immunology/pathology
MH  - Cytokines/metabolism
MH  - Gene Deletion
MH  - *Inflammation/immunology/pathology
MH  - *Inflammatory Bowel Diseases/immunology/pathology
MH  - Mice
MH  - Signal Transduction
MH  - T-Lymphocytes, Regulatory/*immunology
PMC - PMC8877170
EDAT- 2018/08/08 06:00
MHDA- 2019/03/21 06:00
PMCR- 2018/07/31
CRDT- 2018/08/08 06:00
PHST- 2018/08/08 06:00 [pubmed]
PHST- 2019/03/21 06:00 [medline]
PHST- 2018/08/08 06:00 [entrez]
PHST- 2018/07/31 00:00 [pmc-release]
AID - 5062721 [pii]
AID - jjy105 [pii]
AID - 10.1093/ecco-jcc/jjy105 [doi]
PST - ppublish
SO  - J Crohns Colitis. 2018 Nov 28;12(12):1475-1485. doi: 10.1093/ecco-jcc/jjy105.