Cargando…

Understanding inborn errors of immunity: A lens into the pathophysiology of monogenic inflammatory bowel disease

Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal tract, including Crohn’s disease, ulcerative colitis and inflammatory bowel disease-undefined (IBD-U). IBD are understood to be multifactorial, involving genetic, immune, microbial and environmental factors...

Descripción completa

Detalles Bibliográficos
Autor principal: Ouahed, Jodie Deborah
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9556666/
https://www.ncbi.nlm.nih.gov/pubmed/36248828
http://dx.doi.org/10.3389/fimmu.2022.1026511
_version_ 1784807113162227712
author Ouahed, Jodie Deborah
author_facet Ouahed, Jodie Deborah
author_sort Ouahed, Jodie Deborah
collection PubMed
description Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal tract, including Crohn’s disease, ulcerative colitis and inflammatory bowel disease-undefined (IBD-U). IBD are understood to be multifactorial, involving genetic, immune, microbial and environmental factors. Advances in next generation sequencing facilitated the growing identification of over 80 monogenic causes of IBD, many of which overlap with Inborn errors of immunity (IEI); Approximately a third of currently identified IEI result in gastrointestinal manifestations, many of which are inflammatory in nature, such as IBD. Indeed, the gastrointestinal tract represents an opportune system to study IEI as it consists of the largest mass of lymphoid tissue in the body and employs a thin layer of intestinal epithelial cells as the critical barrier between the intestinal lumen and the host. In this mini-review, a selection of pertinent IEI resulting in monogenic IBD is described involving disorders in the intestinal epithelial barrier, phagocytosis, T and B cell defects, as well as those impairing central and peripheral tolerance. The contribution of disrupted gut-microbiota-host interactions in disturbing intestinal homeostasis among patients with intestinal disease is also discussed. The molecular mechanisms driving pathogenesis are reviewed along with the personalized therapeutic interventions and investigational avenues this growing knowledge has enabled.
format Online
Article
Text
id pubmed-9556666
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-95566662022-10-14 Understanding inborn errors of immunity: A lens into the pathophysiology of monogenic inflammatory bowel disease Ouahed, Jodie Deborah Front Immunol Immunology Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal tract, including Crohn’s disease, ulcerative colitis and inflammatory bowel disease-undefined (IBD-U). IBD are understood to be multifactorial, involving genetic, immune, microbial and environmental factors. Advances in next generation sequencing facilitated the growing identification of over 80 monogenic causes of IBD, many of which overlap with Inborn errors of immunity (IEI); Approximately a third of currently identified IEI result in gastrointestinal manifestations, many of which are inflammatory in nature, such as IBD. Indeed, the gastrointestinal tract represents an opportune system to study IEI as it consists of the largest mass of lymphoid tissue in the body and employs a thin layer of intestinal epithelial cells as the critical barrier between the intestinal lumen and the host. In this mini-review, a selection of pertinent IEI resulting in monogenic IBD is described involving disorders in the intestinal epithelial barrier, phagocytosis, T and B cell defects, as well as those impairing central and peripheral tolerance. The contribution of disrupted gut-microbiota-host interactions in disturbing intestinal homeostasis among patients with intestinal disease is also discussed. The molecular mechanisms driving pathogenesis are reviewed along with the personalized therapeutic interventions and investigational avenues this growing knowledge has enabled. Frontiers Media S.A. 2022-09-29 /pmc/articles/PMC9556666/ /pubmed/36248828 http://dx.doi.org/10.3389/fimmu.2022.1026511 Text en Copyright © 2022 Ouahed https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Ouahed, Jodie Deborah
Understanding inborn errors of immunity: A lens into the pathophysiology of monogenic inflammatory bowel disease
title Understanding inborn errors of immunity: A lens into the pathophysiology of monogenic inflammatory bowel disease
title_full Understanding inborn errors of immunity: A lens into the pathophysiology of monogenic inflammatory bowel disease
title_fullStr Understanding inborn errors of immunity: A lens into the pathophysiology of monogenic inflammatory bowel disease
title_full_unstemmed Understanding inborn errors of immunity: A lens into the pathophysiology of monogenic inflammatory bowel disease
title_short Understanding inborn errors of immunity: A lens into the pathophysiology of monogenic inflammatory bowel disease
title_sort understanding inborn errors of immunity: a lens into the pathophysiology of monogenic inflammatory bowel disease
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9556666/
https://www.ncbi.nlm.nih.gov/pubmed/36248828
http://dx.doi.org/10.3389/fimmu.2022.1026511
work_keys_str_mv AT ouahedjodiedeborah understandinginbornerrorsofimmunityalensintothepathophysiologyofmonogenicinflammatoryboweldisease