Th17 or T(h)17, Primary Sclerosing Cholangitis Literature

Primary Sclerosing Cholangitis Literature

Home Page

FAQ

PSC Partners

www Resources

Scientific Literature

Scientific Literature, Th17 or T(h)17

The discovery of IL-23R (interleukin-23 receptor) as a susceptibility gene for several autoimmune/inflammatory diseases is of particular interest because it suggests a critical involvement of interleukin-23 (IL-23) in inflammatory bowel disease, psoriasis, and other inflammatory diseases. Neurath (2007) has suggested that IL-23 be considered as a possible master regulator of Crohn’s disease. The current concept is that IL-23 produced by dendritic cells (DC) in the gut, activates naive T helper (Th) cells and promotes their differentiation into a newly described class of inflammatory T helper cells called Th17 cells (Neurath, 2007; Strober et al., 2007). IL-23R is a receptor that is expressed on Th17 cells. These Th17 cells produce several pro-inflammatory interleukins, including interleukin-17 (IL-17). IL-23 has been identified as a major driver of intestinal inflammation (Hue et al., 2006). Schmechel et al. (2008) have noted that serum interleukin-22 (IL-22) levels are increased in Crohn's disease and correlate with disease activity and IL-23R genotype status, linking genetic CD susceptibility to Th17 cell function for the first time; IL-22 is expressed in IL-23R+ Th17 cells (Schmechel et al., 2008).

Th17 cells have recently been implicated in a number of inflammatory diseases, including experimental models of rheumatoid arthritis and multiple sclerosis. The reader is referred to the following key articles describing these associations: Bettelli et al., 2007; Cooke, 2006; Furuzawa-Carballeda et al., 2007; Iwakura and Ishigame, 2006; Kramer and Gaffen, 2007; Mucida et al., 2007; Sheibanie et al., 2007; Steinman, 2007; Stockinger and Veldhoen, 2007; Weaver et al., 2007.

Th17 cells are a distinct subset of Th cells from the Th1 and Th2 cells described over 20 years ago (Steinman, 2007). Th1 cells produce interferon-gamma, and their differentiation is promoted by interleukin-12 (IL-12). Th2 cells are promoted by interleukin-4 (IL-4). The possible involvement of Th17 cells in inflammatory bowel disease may suggest new therapies, such as antibodies directed against IL-23 (Elson et al., 2007). Knowledge about these cells and the factors that regulate their differentiation, is growing rapidly. Recent studies suggest that prostaglandin E2 and retinoic acid (a metabolite of vitamin A) play key roles in their development and/or activation (Mucida et al., 2007; Sheibanie et al., 2007). Other factors that are known to affect Th17 cell differentiation include interleukin-6 (IL-6), interleukin-27 (IL-27), and interleukin-21 (IL-21) (Korn et al, 2007; Nurieva et al., 2007; Zhou et al., 2007). Mudter and Neurath (2007) propose that IL-6 and Th17 cells may be intimately involved in a vicious circle of T-cell accumulation, finally leading to chronic inflammation. They suggest that this circle can be blocked by anti-IL-6 receptor antibodies. Because Th17 cells have emerged as candidates to account for a number of inflammatory diseases, even cystic fibrosis is being re-evaluated in this light (Dubin et al., 2007).

Number of references = 1400


David and Judy Rhodes Last Update: 3/2/2010