Mucosal Overexpression of Thymic Stromal Lymphopoietin and Proinflammatory Cytokines in Patients With Autoimmune Atrophic Gastritis.
Journal
Clinical and translational gastroenterology
ISSN: 2155-384X
Titre abrégé: Clin Transl Gastroenterol
Pays: United States
ID NLM: 101532142
Informations de publication
Date de publication:
01 07 2022
01 07 2022
Historique:
received:
22
02
2022
accepted:
06
06
2022
entrez:
29
7
2022
pubmed:
30
7
2022
medline:
3
8
2022
Statut:
ppublish
Résumé
The immune mechanisms underlying human autoimmune atrophic gastritis (AAG) are poorly understood. We sought to assess immune mucosal alterations in patients with AAG. In 2017-2021, we collected gastric corpus biopsies from 24 patients with AAG (median age 62 years, interquartile range 56-67, 14 women), 26 age-matched and sex-matched healthy controls (HCs), and 14 patients with Helicobacter pylori infection (HP). We investigated the lamina propria mononuclear cell (LPMC) populations and the mucosal expression of thymic stromal lymphopoietin (TSLP) and nicotinamide phosphoribosyltransferase (NAMPT). Ex vivo cytokine production by organ culture biopsies, under different stimuli (short TSLP and zinc-l-carnosine), and the gastric vascular barrier through plasmalemma vesicle-associated protein-1 (PV1) were also assessed. In the subset of CD19+ LPMC, CD38+ cells (plasma cells) were significantly higher in AAG compared with HC. Ex vivo production of tumor necrosis factor (TNF)-α, interleukin (IL)-15, and transforming growth factor β1 was significantly higher in AAG compared with HC. At immunofluorescence, both IL-7R and TSLP were more expressed in AAG compared with HC and HP, and short TSLP transcripts were significantly increased in AAG compared with HC. In the supernatants of AAG corpus mucosa, short TSLP significantly reduced TNF-α, while zinc-l-carnosine significantly reduced interferon-γ, TNF-α, IL-21, IL-6, and IL-15. NAMPT transcripts were significantly increased in AAG compared with HC. PV1 was almost absent in AAG, mildly expressed in HC, and overexpressed in HP. Plasma cells, proinflammatory cytokines, and altered gastric vascular barrier may play a major role in AAG. TSLP and NAMPT may represent potential therapeutic targets, while zinc-l-carnosine may dampen mucosal inflammation.
Identifiants
pubmed: 35905420
doi: 10.14309/ctg.0000000000000510
pii: 01720094-202207000-00016
pmc: PMC10476748
doi:
Substances chimiques
Cytokines
0
Tumor Necrosis Factor-alpha
0
Carnosine
8HO6PVN24W
Zinc
J41CSQ7QDS
Thymic Stromal Lymphopoietin
GT0IL38SP4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e00510Informations de copyright
Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.
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