Th17 Cells as Potential Probiotic Therapeutic Targets in Inflammatory Bowel Diseases

Abstract

Inflammatory bowel diseases (IBD) are characterized by wasting and chronic intestinal inflammation triggered by various cytokine-mediated pathways. In recent years, it was shown that T helper 17 (Th17) cells are involved in the pathogenesis of IBD, which makes them an attractive therapeutic target. Th17 cells preferentially produce interleukin (IL)-17A–F as signature cytokines. The role of the interplay between host genetics and intestinal microbiota in the pathogenesis of IBD was demonstrated. Probiotics are live microorganisms that when orally ingested in adequate amounts, confer a health benefit to the host by modulating the enteric flora or by stimulating the local immune system. Several studies indicated the effectiveness of probiotics in preventing and treating IBD (ulcerative colitis, and Crohn’s disease). Furthermore, there is mounting evidence of probiotics selectively targeting the Th17 lineage in the prevention and management of inflammatory and autoimmune diseases such as IBD. This review highlights critical roles of Th17 cells in the pathogenesis of IBD and the rationale for using probiotics as a novel therapeutic approach for IBD through manipulation of Th17 cells. The potential molecular mechanisms by which probiotics modulate Th17 cells differentiation and production are also discussed.

Gleaning Insights from Fecal Microbiota Transplantation and Probiotic Studies for the Rational Design of Combination Microbial Therapies

“…Several probiotic strains have been reported to downregulate TNF-␣ and IFN-␥ production in mouse models of colitis, including Lactobacillus brevis SBC 8803, Lactobacillus fermentum, Lactobacillus salivarius subsp. salivarius, Bifidobacterium lactis (243), and mixtures of Lactobacillus and Bifidobacterium species (243,297). S. boulardii also decreases TNF-␣ expression in mice (188).…”

“…Recent evidence also suggests an important role for Th17 cells, a subset of CD4 ϩ T cells that secrete primarily IL-17 (242,243), in UC pathogenesis. Th17 cells and their associated cytokines increase neutrophil recruitment to areas of inflammation, as discussed below; however, the extent to which Th17-associated cytokines such as IL-17A are pathogenic versus protective is controversial (246).…”

“…Indeed, the absence of IL-10 in mouse models significantly increases susceptibility to colitis, and IL-10 supplementation can ameliorate the severity of chemically induced colitis in mice (299,300). Importantly, multiple probiotic species capable of ameliorating disease severity in colitis models, including Lactobacillus species, Bifidobacterium species, and E. coli, increase the production of the anti-inflammatory cytokine IL-10 (301-306) and decrease the expression levels of the inflammatory cytokines TNF-␣ (243) and IFN-␥ (243,297).…”

“…Despite the abundance of pro-and anti-inflammatory cytokines, such as IL-12, TNF-␣, IL-1␤, IL-16, and transforming growth factor ␤ (TGF-␤), that can be found in UC patients (234,237,(239)(240)(241), UC has traditionally been considered a CD4 ϩ T helper cell type 2 (Th2) disease (242,243). This view stemmed from the observation that increased levels of Th2-associated cytokines, including IL-5 and IL-13, can be measured in UC patients and experimental colitis models (239,243,244). Th2-associated cytokines have been shown in some studies to induce damaging effects at the mucosa.…”

Effects of the Sijunzi decoction on the immunological function in rats with dextran sulfate-induced ulcerative colitis

“…IBD are characterized by wasting and chronic intestinal inflammation triggered by various cytokine-mediated pathways (17,18). sIgA has an important role in the intestinal mucosal immunity, which can neutralize viruses, toxins and enzymes and other biological active antigens, and produce a protective effect (19).…”