Interleukin-25

Interleukins (from Latin/Greek inter = between; leukos = white; kinein = to move) is the name given to a group of endogenous, short-chain regulatory proteins (cytokines) of the immune system (IL1-IL38). Interleukins are mediators for induction, progression, and control of T cell-mediated cytotoxic immune responses as well as B cell activation (antibody production). They are predominantly produced and secreted by stimulated leukocytes, monocytes and macrophages. To date, about 38 different interleukins have been clearly identified. Each cytokine of the interleukin group is nomenclatorically assigned a number for its classification (IL-1 to IL-38).

Some structurally related substances have been grouped into families. Their members often have a similar function or participate in the fine regulation of immune responses, for example, by regulating the synthesis of related interleukins. Interleukin-25 is a pro-inflammatory cytokine that belongs to the interleukin-17 family along with interleukins IL-17, IL-21, and IL-22. Interleukin-25 binds to its receptor IL-25R.

Interleukin-25 belongs to the interleukin-17 family. It is homologous to IL- 17E and influences immunological processes of Th2 immunity (see below Interleukin-17). Both cytokines are ligands for the cytokine receptor IL-17RB. IL-25 induces the expression of other cytokines, such as IL-4, IL-5, IL-8 and IL-13.

The cytokine is produced and secreted by type 2 helper T cells, mast cells, and eosinophilic granulocytes. Its expression can be induced by allergens as well as helminthic parasites.

Together with its receptor, IL-25 plays an important role in the modulation of the type 2 immune response, especially pro-inflammatory functions of eosinophilic granulocytes in allergic bronchial asthma and other allergic diseases such as chronic rhinosinusitis with nasal polyps (CRSwNP). Thus, plasma levels of IL-25 and IL-25R (IL-17RA/IL-17RB/IL-17RA/RB) are elevated in patients with allergic bronchial asthma.

Although IL-25 and IL-17 are members of the same cytokine family, both cytokines appear to play opposite roles in the pathogenesis of autoimmune diseases. IL-25 is involved in the pathogenetic course of allergic processes. In a second function (note: detectable dualism of many cytokines) IL-25 controls and reduces Th1/Th17-triggered immunological processes.

IL-25 is a cytokine that controls intestinal immunity. It is involved in the chronic inflammatory processes of the intestine. Furthermore, the cytokine has an antitumor effect, which has been shown in a number of malignancies, such as pancreatic, colon, lung and mammary carcinomas.

1. Benatar T et al(2010) IL-17E, a proinflammatory cytokine, has antitumor efficacy against several tumor types in vivo. Cancer immunology, immunotherapy. 59: 805–817.
2. Büning C et al(2003) The interleukin-25 gene located in the inflammatory bowel disease (IBD) 4 region: no association with inflammatory bowel disease. European Journal of Immunogenetics 30: 329-333.
3. Caruso R, et al. (2011) The dual role of interleukin-25 in the control of immune-mediated pathologies. Curr Mol Med 11:26-30.
4. Cheung J et al (2001) IL-25 induces IL-4, IL-5, and IL-13 and Th2-associated pathologies in vivo. Immunity 15: 985-995.
5. Furuta S et al (2011) "IL-25 causes apoptosis of IL-25R-expressing breast cancer cells without toxicity to nonmalignant cells". Science Translational Medicine 3: 78ra31.
6. Iinuma T et al (2015) Interleukin-25 and mucosal T cells in noneosinophilic and eosinophilic chronic rhinosinusitis. Ann Allergy Asthma Immunol 114:289-
7. Ikeda K et al (2003) Mast cells produce interleukin-25 upon Fc epsilon RI-mediated activation. Blood 101: 3594-3596.
8. Kim MR et al (2002) Transgenic overexpression of human IL-17E results in eosinophilia, B-lymphocyte hyperplasia, and altered antibody production. Blood 100: 2330-2340.
9. Lee J et al (2001) IL-17E, a novel proinflammatory ligand for the IL-17 receptor homolog IL-17Rh1. The Journal of Biological Chemistry 276: 1660-1664.
10. Owyang AM et al.(2006) "Interleukin 25 regulates type 2 cytokine-dependent immunity and limits chronic inflammation in the gastrointestinal tract". The Journal of Experimental Medicine 203: 843-849.
11. Saadoun D et al (2011) Interleukin-25: key regulator of inflammatory and autoimmune diseases. Curr Pharm Des 17:3781378-5.