Interleukin-19 contributes as a protective factor in experimental Th2-mediated colitis

Abstract

Inflammatory bowel disease results from chronic dysregulation of the mucosal immune system and aberrant activation of both the innate and adaptive immune responses. IL-19 is a member of the IL-10 family, and IL-10 plays an important role in inflammatory bowel disease. We have previously shown that IL-19 knockout mice are more susceptible to innate-mediated colitis. Next, we ask whether IL-19 contributes to T cells-mediated colitis. Here, we investigated the role of IL-19 in a mouse model of Th2 cell-mediated colitis. Inflammatory responses in IL-19-deficient mice were assessed using a Th2-mediated colitis induced by oxazolone. The colitis was evaluated by analyzing the body weight loss and histology of the colon. Lymph node cells were cultured in vitro to determine cytokine production. IL-19 knockout mice exacerbated oxazolone-induced colitis by stimulating the transport of inflammatory cells into the colon, and by increasing IgE production and the number of circulating eosinophil. The exacerbation of oxazolone-induced colonic inflammation following IL-19 knockout mice was accompanied by an increased production of IL-4 and IL-9, but no changes in the expression of IL-5 and IL-13 in lymph node cells. IL-19 plays an anti-inflammatory role in the Th2-mediated colitis model, suggesting that IL-19 may represent a potential therapeutic target for reducing colonic inflammation.

The Role of Interleukin-19 in Contact Hypersensitivity

“…10) Heterozygous mice were crossed to produce IL-19KO and wild-type (WT) control mice. All mice used were 8-15 weeks old.…”

“…7) We previously generated IL-19 deficient (IL-19 knock out (KO)) mice that demonstrate, in vivo, the importance of inflammatory bowel disease and, in vitro, the significance of macrophage function. [8][9][10] [17][18][19] The psoriatic epidermis has high IL-19 expression, 19) and IL-19 released by keratinocytes upregulates the production of keratinocyte growth factor from CD8 + T cells, which form a positive feedback loop that exacerbates psoriasis. 18) Thus, IL-19 regulates the development of psoriasis through the facilitation of the Th1 response.…”

Exacerbated experimental pancreatitis in interleukin-19 knockout mice

“…Recent studies have shown that IL-19 was produced by keratinocytes [3,4], epithelial cells [5][6][7][8], macrophages [9,10], B cells [11,12], and vascular smooth muscle cells [13]. Our previous studies showed that IL-19-knockout (KO) mice were more susceptible to experimental acute colitis induced by dextran sulfate sodium, TNBS, and oxazolone [10,14,15]. These results indicate that IL-19 plays as the anti-inflammatory effector.…”

Interleukin-19 enhances cytokine production induced by lipopolysaccharide and inhibits cytokine production induced by polyI:C in BALB/c mice

“…We used IL-19KO mice on a BALB/c background [11,12]. Heterozygous mice were crossed to produce IL-19KO and WT control mice.…”