Effector and suppressor T cells in celiac disease

Abstract

Celiac disease (CD) is a T-cell mediated immune disease in which gliadin-derived peptides activate lamina propria effector CD4+ T cells. This activation leads to the release of cytokines, compatible with a Th1-like pattern, which play a crucial role in the pathogenesis of CD, controlling many aspects of the inflammatory immune response. Recent studies have shown that a novel subset of effector T cells, characterized by expression of high levels of IL-17A, termed Th17 cells, plays a pathogenic role in CD. While these effector T cell subsets produce proinflammatory cytokines, which cause substantial tissue injury in vivo in CD, recent studies have suggested the existence of additional CD4⁺ T cell subsets with suppressor functions. These subsets include type 1 regulatory T cells and CD25⁺CD4⁺ regulatory T cells, expressing the master transcription factor Foxp3, which have important implications for disease progression.

Keywords: Celiac disease; Th1 cells; Th17 cells; Treg cells

Core tip: Although it is evident that effector gliadin-specific Th1 cells play an important role in celiac disease (CD) pathogenesis, recent studies have implicated Th17 effector cells in the disease process. Contrasting evidence has been reported on the ability of gliadin-specific cells to produce IL-17A. In addition, regulatory T cells, formerly known as suppressor T cells, have been identified in intestinal biopsy specimens of patients with active CD. Nevertheless, despite the presence of an endogenous counter-regulatory mechanism in the intestinal mucosa of celiac patients, the inflammatory response is not suppressed. In this review, we provide an overview of the current knowledge of the contribution of both Th1 and Th17 effector T cells and Treg cells in controlling mucosal inflammation in CD.