Recombinant Human IL-25/IL-17E

Interleukin-25 (IL-25), which is also known as IL-17E, promotes Th2-biased immune responses. This is in contrast to other IL-17 family members which promote Th1- and Th17-biased inflammation. IL-25 is an important mediator of allergic reactions and protection against intestinal parasites ^{[1, 2]}. Mature human IL-25 shares 80% amino acid sequence identity with mouse and rat IL-25 ^{[3, 4]}. During helminth infections and allergic reactions, IL-25 is locally up-regulated in intestinal and airway epithelial cells, atopic dermatitis skin lesions, and local Th2 cells, eosinophils, and basophils ^[4-9]. It binds to IL-17 RB but also requires IL-17 RA to exert its activity ^{[3, 8, 10]}. IL-25 acts on a variety of cell types which respond with increased production of Th2 cytokines (e.g. IL-4, IL-5, IL-13) and reduced production of Th1 and Th17 cytokines (e.g. IFN-gamma, IL-12, IL-23, IL-17A, IL-17F) ^{[4-6, 8, 9, 11-15]}. Airway IL-25 can be activated by MMP-7, a protease that is up-regulated in airway epithelium in response to allergen exposure ^[16]. Cleaved IL-25 shows enhanced binding to IL-17 RB and stronger induction of Th2 cytokines ^[16]. The Th2 cytokines, in turn, trigger expansion of Th2 memory cells and anti-inflammatory M2 macrophages, increased eosinophil mobilization and activation, and dendritic cell migration ^{[4, 6, 9, 13]}. These actions promote protective anti-helminth immune responses ^{[4, 5]} as well as allergic inflammation and airway hyperreactivity ^[11]. The IL-25 induced suppression of Th1 and Th17 cytokines limits Th17 cell expansion and disease pathology in autoimmunity and colitis ^{[12, 14]}.

Reference

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[7]. Corrigan, C.J. et al. (2011) Proc. Natl. Acad. Sci. USA 108:1579.

[8]. Petersen, B.C. et al. (2012) Nat. Med. 18:751.

[9]. Wang, Y.-H. et al. (2007) J. Exp. Med. 204:1837.

[10]. Rickel, E.A. et al. (2008) J. Immunol. 181:4299.

[11]. Hurst, S.D. et al. (2002) J. Immunol. 169:443.

[12]. Kleinschek, M.A. et al. (2007) J. Exp. Med. 204:161.

[13]. Cao, Q. et al. (2011) J. Am. Soc. Nephrol. 22:1229.

[14]. Stock, P. et al. (2009) J. Immunol. 182:5116.