Contribution of the IL-17/IL-23 axis to the pathogenesis of inflammatory bowel disease

Abstract

Inflammatory bowel diseases (IBDs) are chronic disorders of modern society, requiring management strategies aimed at prolonging an active life and establishing the exact etiology and pathogenesis. These idiopathic diseases have environmental, genetic, immunologic, inflammatory, and oxidative stress components. On the one hand, recent advances have shown that abnormal immune reactions against the microorganisms of the intestinal flora are responsible for the inflammation in genetically susceptible individuals. On the other hand, in addition to T helper cell-type (Th) 1 and Th2 immune responses, other subsets of T cells, namely regulatory T cells and Th17 maintained by IL-23 are likely to develop IBD. IL-23 acts on innate immune system members and also facilitates the expansion and maintenance of Th17 cells. The IL-17/IL-23 axis is relevant in IBD pathogenesis both in human and experimental studies. Novel biomarkers of IBD could be calprotectin, microRNAs, and serum proinflammatory cytokines. An efficient strategy for IBD therapy is represented by the combination of IL-17A and IL-17F in acute IL-17A knockout TNBS-induced colitis, and also definite decrease of the inflammatory process in IL-17F knockout, DSS-induced colitis have been observed. Studying the correlation between innate and adaptive immune systems, we hope to obtain a focused review in order to facilitate future approaches aimed at elucidating the immunological mechanisms that control gut inflammation.

Profile of interleukin-22 in gut mucosal health and disease

“…127 It is also important to note that Th17 cells can produce both IL-22 and IL-17, with the latter also being associated with the IBD pathogenesis. 126 Moreover, a recent study demonstrated that IFN-γ/IL-17-coproducing CD4+ T-cells specifically enriched in the inflamed mucosal tissue of patients with IBD also showed high expression levels of However, data from mouse models support an important protective role of IL-22 in IBD. 35,129 In humans, a loss of the Th22 subset has been reported in the colon of patients with UC, 130 whereas IL-22 production by ILCs has been seen to be impaired in inflamed tissue of patients with CD; 58 increased production of IL-22BP, a negative regulator of IL-22 function, has also been observed in human IBD.…”

“…Evidence supports a role of IL-22 in driving IBD, through its ability to function as a proinflammatory cytokine. [123][124][125] Certainly, IL-23, a potent inducer of IL-22 production, 4 has a key role, 126 with an expansion of IL-23-responsive ILCs observed in the context of IBD. 127 It is also important to note that Th17 cells can produce both IL-22 and IL-17, with the latter also being associated with the IBD pathogenesis.…”

Th‐17 response and antimicrobial peptide expression are uniformly expressed in gastric mucosa of Helicobacter pylori‐infected patients independently of their clinical outcomes

“…The s1/i1/m1 genotype of vacA is strongly associated with precancerous and cancerous gastric diseases . In relation to host inflammatory response, genetic polymorphisms in genes encoding IL‐1β, IL‐1RA, CXCL‐8, tumor necrosis factor alpha (TNFα), IL‐10, IL‐17A, IL‐17F, and IL‐23R have been linked to severe gastroduodenal diseases and particularly to precancerous lesions, suggesting that variations in the inflammatory response to the chronic H. pylori infection directly impact the initiation and progression of gastric diseases …”

“…8,9 In relation to host inflammatory response, genetic polymorphisms in genes encoding IL-1β, IL-1RA, CXCL-8, tumor necrosis factor alpha (TNFα), IL-10, IL-17A, IL-17F, and IL-23R have been linked to severe gastroduodenal diseases and particularly to precancerous lesions, suggesting that variations in the inflammatory response to the chronic H. pylori infection directly impact the initiation and progression of gastric diseases. [10][11][12][13] Due to its central role in H. pylori infection, the intensity of inflammatory response has been proposed as an explanation for clinical outcome determinism. Inflammatory response to H. pylori infection has been widely explored in animal models and in vitro experiments using cancerous gastric cell lines.…”

Increased CD4+CD45RA-FoxP3lowcells alter the balance between Treg and Th17 cells in colitis mice

“…Acquired immunity plays a vital role in UC pathogenesis, where in T helper cell-type (Th) 1 and Th2 immune responses, as well as alternate subsets of T cells, such as regulatory T cells (Treg) and T helper 17 (Th17) cells, contribute to IBD[4,5]. …”