Work

A Mouse Model for Generation of Gut Lamina Propria Plasma Cells Specific for a Deamidated Gluten Peptide

Year: 2025

Type: article

Abstract: ABSTRACT Celiac disease is an autoimmune enteropathy caused by aberrant immune responses to dietary gluten peptides. Plasma cells (PCs) reactive with deamidated gluten peptides (DGP) or transglutaminase 2 are abundant in celiac disease gut lesions, yet their role in disease pathogenesis remains unclear. Here, we present a mouse model that allows for exploring the role of DGP‐specific IgA PCs. This model employs a novel immunoglobulin knock‐in (Ig KI) mouse expressing a celiac‐patient‐derived anti‐DGP B‐cell receptor (BCR) that recognizes an immunodominant DGP epitope. In these mice, ∼80% of splenic B cells express the transgenic BCR. In co‐culture experiments with transgenic DGP‐specific B cells and transgenic gluten‐specific CD4 + T cells, stimulation with DGP led to T‐cell and B‐cell proliferation. Mice carrying the celiac disease‐associated human leukocyte antigen (HLA) allotype HLA‐DQ2.5 developed DGP‐specific small intestinal IgA PCs upon adoptive transfer of HLA‐DQ2.5‐expressing DGP‐specific B cells and oral immunizations with DGP and cholera toxin (CT). However, covalent conjugation of DGP to CT was required for effective anti‐DGP gut immunity. This novel mouse model provides an important tool for studying the role of PCs beyond antibody production in celiac disease.

Source: European Journal of Immunology

DOI: 10.1002/eji.202451658

Authors: Runa I. Løberg, Alisa E. Dewan, Liv Kleppa, M. Fleur du Pré, Ludvig M. Sollid

Institutions: Oslo University Hospital, University of Oslo

Language: English

Topic: Celiac Disease Research and Management

Subfield: Gastroenterology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: bronze

Funder: Norges Forskningsråd