PMID- 30898172
OWN - NLM
STAT- MEDLINE
DCOM- 20190820
LR  - 20200225
IS  - 1824-7288 (Electronic)
IS  - 1720-8424 (Linking)
VI  - 45
IP  - 1
DP  - 2019 Mar 21
TI  - The gliadin-CFTR connection: new perspectives for the treatment of celiac 
      disease.
PG  - 40
LID - 10.1186/s13052-019-0627-9 [doi]
LID - 40
AB  - Familial loss-of-function mutations of the gene coding for the cystic fibrosis 
      transmembrane conductance regulator (CFTR) channel protein cause cystic fibrosis 
      (CF), the most frequent inherited life-threatening disease in the Caucasian 
      population. A recent study indicates that the gluten/gliadin-derived peptide 
      (P31-43) can cause CFTR inhibition in intestinal epithelial cells, thus causing a 
      local stress response that contributes to the immunopathology of celiac disease 
      (CD). Accordingly, an increased prevalence of CD has been observed in several 
      cohorts of CF patients. CD is characterized by a permanent intolerance to 
      gluten/gliadin proteins occurring in a proportion of susceptible individuals who 
      bear the human leukocyte antigen (HLA) DQ2/DQ8. In CD, perturbations of the 
      intestinal environment, together with the activation of the innate immune system 
      by P31-43, are essential for rendering other immunodominant gliadin peptide fully 
      antigenic, thus triggering an adaptive immune response with an autoimmune 
      component. P31-43-induced CFTR inhibition elicits the danger signals that ignite 
      the epithelial stress response and perturb epithelial proteostasis. Importantly, 
      potentiators of CFTR channel gating, such as the FDA-approved drug Ivacaftor, 
      prevent P31-43 driven CFTR inhibition and suppress the gliadin-induced stress 
      response in cells from celiac patients, as well as the immunopathology developing 
      in gliadin-sensitive mice. Thus, CFTR potentiators may represent a novel 
      therapeutic option for celiac patients.
FAU - Maiuri, Luigi
AU  - Maiuri L
AUID- ORCID: 0000-0002-4962-9016
AD  - Department of Health Sciences, University of Eastern Piedmont, Novara, Italy.
AD  - European Institute for Research in Cystic Fibrosis, San Raffaele Scientific 
      Institute, Milan, Italy.
FAU - Villella, Valeria R
AU  - Villella VR
AD  - Department of Health Sciences, University of Eastern Piedmont, Novara, Italy.
FAU - Raia, Valeria
AU  - Raia V
AD  - Regional Cystic Fibrosis Center, Pediatric Unit, Department of Translational 
      Medical Sciences, Federico II University Naples, Naples, Italy.
FAU - Kroemer, Guido
AU  - Kroemer G
AD  - Equipe11 labellisee Ligue Nationale contrele Cancer, Centre de Recherche des 
      Cordeliers, Paris, France. kroemer@orange.fr.
AD  - INSERM U1138, Centre de Recherche des Cordeliers, Paris, France. 
      kroemer@orange.fr.
AD  - Universite Paris Descartes, Paris, France. kroemer@orange.fr.
AD  - Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, Villejuif, 
      France. kroemer@orange.fr.
AD  - Pole de Biologie, Hopital Europeen Georges Pompidou, AP-HP, Paris, France. 
      kroemer@orange.fr.
AD  - Karolinska Institute, Department of Women's and Children's Health, Karolinska 
      University Hospital, 17176, Stockholm, Sweden. kroemer@orange.fr.
LA  - eng
PT  - Editorial
DEP - 20190321
PL  - England
TA  - Ital J Pediatr
JT  - Italian journal of pediatrics
JID - 101510759
RN  - 0 (Aminophenols)
RN  - 0 (CFTR protein, human)
RN  - 0 (Chloride Channel Agonists)
RN  - 0 (Quinolones)
RN  - 126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator)
RN  - 1Y740ILL1Z (ivacaftor)
RN  - 9007-90-3 (Gliadin)
MH  - Adaptive Immunity
MH  - Aminophenols/therapeutic use
MH  - Celiac Disease/drug therapy/*immunology
MH  - Chloride Channel Agonists/therapeutic use
MH  - Cystic Fibrosis Transmembrane Conductance Regulator/antagonists & 
      inhibitors/*immunology
MH  - Epithelial Cells/immunology
MH  - Gliadin/*immunology
MH  - Humans
MH  - Intestinal Mucosa/immunology/pathology
MH  - Quinolones/therapeutic use
PMC - PMC6429699
OTO - NOTNLM
OT  - CFTR
OT  - Celiac disease
OT  - Gliadin
COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: Not applicable. CONSENT FOR 
      PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they 
      have no competing interests. A patent application by LM is pending (filing date, 
      July 26, 2017. No 102017000085714). GK is a scientific co-founder of Samsara 
      therapeutics. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to 
      jurisdictional claims in published maps and institutional affiliations.
EDAT- 2019/03/23 06:00
MHDA- 2019/08/21 06:00
PMCR- 2019/03/21
CRDT- 2019/03/23 06:00
PHST- 2019/02/12 00:00 [received]
PHST- 2019/02/27 00:00 [accepted]
PHST- 2019/03/23 06:00 [entrez]
PHST- 2019/03/23 06:00 [pubmed]
PHST- 2019/08/21 06:00 [medline]
PHST- 2019/03/21 00:00 [pmc-release]
AID - 10.1186/s13052-019-0627-9 [pii]
AID - 627 [pii]
AID - 10.1186/s13052-019-0627-9 [doi]
PST - epublish
SO  - Ital J Pediatr. 2019 Mar 21;45(1):40. doi: 10.1186/s13052-019-0627-9.