Association between innate response to gliadin and activation of pathogenic T cells in coeliac disease

Gluten induces coeliac-like disease in sensitised mice involving IgA, CD71 and transglutaminase 2 interactions that are prevented by probiotics

“…1,5 Increased accumulation of CD11b þ macrophages was observed in the lamina propria of the G þ mice (Figure 5c; Po0.05), and this accumulation was associated with an increased number of IL-15 þ , TNF-a þ and COX-2 þ cells (Figure 5d; Po0.01). In contrast, there were no changes in the number of COX-1 þ cells (Figure 5d).…”

“…The retrotranscytosis of IgA-gliadin complexes may trigger both innate and adaptive immune responses, which initiate CD enteropathy. 5 In particular, in the lamina propria, gliadin peptides activate tissue TG2, the coeliac autoantigen, 6 which selectively deamidates the gluten protein resulting in CD4 þ T-cell activation. These cells release mediators, such as interferon-g (IFN-g), 7 tumour necrosis factor-a (TNF-a) 7 and interleukin (IL)-10, 8 which ultimately cause tissue damage and the production of autoantibodies.…”

Early tissue transglutaminase–mediated response underlies K562(S)-cell gliadin-dependent agglutination

“…Blocking TG2 activation, a central player of these cell surface events (14), by means of the Ca 2+ chelator BAPTA-AM or the anti-TG2 antibody CUB 7402 prevented the early rearrangement of the actin fibers occurring after a few minutes of gliadin challenge (Figure 4a). In recent years, a growing body of evidence has highlighted the ability of some gliadin peptides, such as gliadin-derived peptide 31-43 (p31-43), to specifically elicit a mucosal innate activation in celiac duodenum as well as in intestinal epithelial cell lines (6). To assess whether p31-43 could recapitulate the surface effects of the whole gliadin digests and trigger K562(S)-cell agglutination, we incubated K562(S) cells with p31-43 or the immunodominant pα-9 gliadin peptide, ineffective in inducing an innate response (6).…”

“…Despite this unassailable evidence, a series of studies have indicated that T cells, although essential for the full CD manifestation, cannot explain all the facets of CD (4,5). These studies have suggested that different portion(s) of gliadin, ostensibly not the ones recognized by T cells, modulate an innate activation of celiac small intestine that sets the tone and intensity of the adaptive immune response induced by the immunodominant gliadin epitopes (6). Surprisingly, gliadin and prolamin preparations also show biological activity on celiac-unrelated in vitro systems, including intestinal epithelial cells lines, fetal rat jejunum, and K562(S) cells, a highly undifferentiated cell line isolated from an outgrowth of a patient with chronic myelogenous leukemia (7)(8)(9).…”

Celiac Disease with Pure Red Cell Aplasia: An Unusual Hematologic Association in Pediatric Age Group

“…Paracellular passage of gliadin peptides (a-gliadin 31-43) has been shown to induce apoptosis of enterocytes, upregulate MHC class I molecules, activate MAP kinase pathway, and upregulate expression of CD83, a maturation marker of dendritic cells [9,10]. This peptide, and others, enhances IL15 production leading to an expansion of intraepithelial lymphocytes (IELs) and triggering the innate immune system.…”