Mast cells are associated with the onset and progression of celiac disease - 19/04/17
Abstract |
Background |
Celiac disease (CD) is an immune-mediated disorder characterized by an accumulation of immune cells in the duodenal mucosa as a consequence of both adaptive and innate immune responses to undigested gliadin peptides. Mast cells (MCs) are innate immune cells that are a major source of costimulatory signals and inflammatory mediators in the intestinal mucosa. Although MCs have previously been associated with CD, functional studies have never been performed.
Objective |
We aimed at evaluating the role of MCs in the pathogenesis of CD.
Methods |
Intestinal biopsy specimens of patients with CD were scored according to the Marsh classification and characterized for leukocyte infiltration and MC distribution. Moreover, MC reactivity to gliadin and its peptides was characterized by using in vitro assays.
Results |
Infiltrating MCs were associated with the severity of mucosal damage, and their numbers were increased in patients with higher Marsh scores. MCs were found to directly respond to nonimmunodominant gliadin fragments by releasing proinflammatory mediators. Immunohistochemical characterization of infiltrating MCs and the effects of gliadin peptides on intestinal MCs indicated an increase in proinflammatory MC function in advanced stages of the disease. This was also associated with increased neutrophil accumulation, the prevalence of M1 macrophages, and the severity of tissue damage.
Conclusion |
We provide a description of the progressive stages of CD, in which MCs are the hallmark of the inflammatory process. Thus the view of CD should be revised, and the contribution of MCs in the onset and progression of CD should be reconsidered in developing new therapeutic approaches.
Le texte complet de cet article est disponible en PDF.Key words : Celiac disease, mast cell, gliadin immunology, p31-43 fragment
Abbreviations used : BMMC, CD, CM-H2DCFDA, Foxp3, MC, MFI, MyD88, NAC, NF-κB, ROS, TLR, Treg, WT
Plan
| Supported by COST Action BM1007 “Mast cells and basophils: targets for innovative therapies,” Italian Ministry of Health, (nos. 15561 and 11843), Ministero dell'Istruzione, Università e Ricerca (PRIN2009), and ASIMAS (ASsociazione Italiana MAStocitosi). |
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| Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest. |
Vol 139 - N° 4
P. 1266 - avril 2017 Retour au numéro
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