Mucosal overexpression of thymic stromal lymphopoietin and pro-inflammatory cytokines in patients with autoimmune atrophic gastritis

Abstract

The immune mechanisms underlying human autoimmune atrophic gastritis (AAG) are poorly understood. We sought to assess immune mucosal alterations in AAG patients.

METHODS: 

In 2017-2021, we collected gastric corpus biopsies from 24 AAG patients (median age 62 years, IQR 56-67, 14 females), 26 age- and sex-matched healthy controls (HC), and 14 patients with H. 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.

RESULTS: 

In the subset of CD19+ LPMC, CD38+ cells (plasma cells) were significantly higher in AAG compared to HC. Ex vivo production of TNF-α, IL-15, and TGF-β1 was significantly higher in AAG compared to HC. At immunofluorescence, both IL-7R and TSLP were more expressed in AAG compared to HC and HP, and short TSLP transcripts were significantly increased in AAG compared to HC. In the supernatants of AAG corpus mucosa, short TSLP significantly reduced TNF-α, while zinc-l-carnosine significantly reduced IFN-ɣ, TNF-α, IL-21, IL-6, and IL-15. NAMPT transcripts were significantly increased in AAG compared to HC. PV1 was almost absent in AAG, mildly expressed in HC, and over-expressed in HP.

Plasma cells, pro-inflammatory 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.