Role of type 2 immunity in intestinal inflammation

Abstract

Purpose of Review Type 2 (Th2) immune responses play important roles in intestinal immunity by contributing to the maintenance of mucosal homeostasis, conferring protection against helminthic inflection, but also participating in pro-inflammatory pathways in chronic intestinal inflammatory disorders, including inflammatory bowel disease (IBD). The current review focuses on recent developments regarding the role of type 2 responses in intestinal inflammation. Recent Findings Th2 gut mucosal responses are promoted by mediators that are released following injury to the epithelium and act as alarmin-type danger signals. IL-33 is prominent among such factors and demonstrates a dichotomous function exerting either protective or pro-inflammatory effects, depending on its cellular compartmentalization. The pool of type 2 effector cells has been enriched recently to include not only classical CD4+ Th2 lymphocytes but also a subset of innate lymphocytes (ILC2) that express the transcriptional factor GATA3 and secrete IL-4, IL-5, and IL-13. ILC2 play important roles during infection with helminthes and bi-directionally interact with Th2 CD4+ lymphocytes, thus, establishing a transition from innate to adaptive immunological pathways. Type 2 responses are also involved in pro-inflammatory pathways at the intestinal mucosa and neutralization of the pivotal cytokines IL-4 and IL-13 has been shown to regulate experimental intestinal inflammation. In striking contrast, however, neutralization of human IL-13 had no therapeutic effect in patients with ulcerative colitis. Summary Further studies will be required to delineate the specific mechanisms of type 2 mucosal immunity in IBD and examine the applicability of Th2-targeted therapies for intestinal inflammation.

Casticin prevents DSS induced ulcerative colitis in mice through inhibitions of NF‐κB pathway and ROS signaling

“…Understanding the mechanism of proinflammatory cytokines expressions is crucial to the development of therapeutic drugs for UC. Studies revealed that proinflammatory cytokines such as IL‐1β, IL‐6, TNF‐α, and IL‐17 are key mediators and initiators in the inflammation of colon in UC (Bamias & Cominelli, ; Catana et al, ; Chen & Sundrud, ; Fantini & Pallone, ). And transcriptions of these proinflammatory cytokines are dependent on the activation of NF‐κB pathway (Atreya, Atreya, & Neurath, ; Merga et al, ).…”

Interleukin-4 Inhibits Regulatory T Cell Differentiation through Regulating CD103+ Dendritic Cells

“…Beyond that, type 2 immune response is also involved in the process of wound healing in the gut (32, 33). Nevertheless, dysregulated and overreactive Th2 immunity may lead to detrimental inflammation.…”

Lamina propria group 2 innate lymphoid cells impair the antibacterial defense of burned mice to enterococcal translocation

“…ILC2 are phenotypically demarcated from other lymphoid cells by the absence of conventional lin markers (for B, T, myeloid, and erythroid cells), in combination with the expression of ICOS, Sca-1, CD127, CD25, and receptors for IL-25 (IL17BR) and IL-33 (T1/ST2) by flow cytometry [33]. Following previous descriptions [24][25][26][27]33], lin 2 CD127 + ICOS + Sca-1 + cells, with an ability to produce IL-5 and IL-13, have been classified as ILC2. In adoptive-transfer experiments, ILC2 were sorted from pooled lamina propria mononuclear cells obtained from 25 burned mice and adjusted to 1 3 10 7 cells/ml in PBS.…”

“…Type 2 cytokines (IL-4, IL-5, IL-9, IL-10, and IL-13), produced by type 2 cells (Th2 cells [19], M2Mf [20][21][22], and PMN-II [23]), play a role in the increased susceptibility of severely burned hosts to opportunistic infections. In addition, ILC2 have recently been described to be critical in the development of type 2 immune responses [24][25][26][27]. ILC2 are one of the family of ILCs consisting of 3 groups: ILC1 (NK cells and ILC1), ILC2, and ILC3 (natural cytotoxic receptor 2/+ ILC3 and lymphoid tissue inducer cells) [26].…”

“…ILC3 maintain gastrointestinal mucosal barrier [24,28,29] through the productions of IL-17A and IL-22. ILC2, commonly distributed in blood, lung, and intestine, are cells to produce high levels of type 2 cytokines [24][25][26][27].…”