Regulatory T cells as a therapeutic approach for inflammatory bowel disease

Abstract

Foxp3 + T regulatory (Treg) cells suppress inflammation and are essential for maintaining tissue homeostasis. A growing appreciation of tissue-specific Treg functions has built interest in leveraging the endogenous suppressive mechanisms of these cells into cellular therapeutics in organ-specific diseases. Notably, Treg cells play a critical role in maintaining the intestinal environment. As a barrier site, the gut requires Treg cells to mediate interactions with the microbiota, support barrier integrity, and regulate the immune system. Without fully functional Treg cells, intestinal inflammation and microbial dysbiosis ensue. Thus, there is a particular interest in developing Treg cellular therapies for intestinal inflammatory disease, such as inflammatory bowel disease (IBD). This article reviews some of the critical pathways that are dysregulated in IBD, Treg cell mechanisms of suppression, and the efforts and approaches in the field to develop these cells as a cellular therapy for IBD.

Allergic Airway Inflammation Emerges from Gut Inflammation and Leakage in Mouse Model of Asthma

“…In addition to the increase in percentages of gut Th2 cells, regulatory T cells (Tregs) are found to be declining in their percentages in pre‐ and post‐challenge conditions both in gut and lung tissues compared to the control groups (Figure S1, Supporting Information). This data is supported by previous studies demonstrating reduced numbers and functions of Tregs both in inflammatory intestinal diseases [ 38,39 ] and in allergic asthma. [ 40,41 ] However, adoptive transfer of Treg cells in a mouse model of asthma did not satisfactorily resolve the disease, suggesting a contradictory role of Tregs in allergic airway inflammation.…”

Oxidative Stress, Inflammation, Gut Dysbiosis: What Can Polyphenols Do in Inflammatory Bowel Disease?

“…The ratio of Treg/Th17 affects the outcomes of inflammation [ 140 ]. As the most important counterbalance to the proinflammatory environment of the immune system, Treg cells secrete cytokines such as TGF-β and IL-10 to mediate tissue repair and epithelial cell differentiation and interact with APCs to suppress inflammation and maintain intestinal homeostasis [ 141 , 142 ]. These immune cells are triggered by DAMPs or PAMPs and interact with varying function, leading to alterations in the immune tolerance environment, thereby causing persistent oxidative stress and inflammation and subsequent tumorigenesis in the gut [ 143 , 144 ].…”

A Pro‐Regenerative Supramolecular Prodrug Protects Against and Repairs Colon Damage in Experimental Colitis

“…Recently Foxp3 + Tregs have been shown to aid in epithelial repair in experimental colitis, and Treg cell suppression or dysfunction is known to accelerate lesion formation in clinical IBD. [ 34 , 35 , 36 ] Thus, HIF‐1α‐orchestrated recruitment of Tregs to active ulcers may directly contribute to healing in DPCA‐treated mice.…”