Interleukin 27
Interleukin 27 (IL-27) is a member of the IL-12 cytokine family. It is a heterodimeric cytokine that is composed of two distinct genes, Epstein-Barr virus-induced gene 3 (EBI3) and IL-27p28. IL-27 is expressed by antigen presenting cells and interacts with a specific cell-surface receptor complex known as IL-27 receptor (IL-27R).[1][2][3][4][5] This receptor consists of two proteins, IL-27ɑ and gp130. IL-27 induces differentiation of the diverse populations of T cells in the immune system and also upregulates IL-10.
Signal Transduction
When IL-27 binds to the IL-27 receptor, signaling pathways including JAK-STAT and p38 MAPK pathways are turned on.[2] There are two types of responses, pro-inflammatory and anti-inflammatory, which involve different types of cells, such as macrophages, dendritic cells, T cells, and B cells.[3] The response that is activated is very much dependent on the external surrounding of IL-27.[1][2][3]
Differentiation of T cells
There are many different subsets of T cells, such as Th1, Th2, Th17, Tr1, and Treg cells; IL-27 is greatly involved in differentiation through inducing or suppressing of each T cell subset.[1][2][4][5] Th1 cells, which express IFNγ, are promoted by IL-27 through STAT1 and T-bet activation. Th2 cells, which express IL-4, are inhibited by IL-27 through the transcription factor GATA-3. Th17 cells, which express IL-17, IL-22, and granulocyte macrophage colony-stimulating factor (GM-CSF), are inhibited by IL-27 through STAT1 and expression of transcription factor RORγt. Tr1 cells, which express IL-10, are induced by IL-27 through the transcription factor c-Maf. Treg cells are inhibited by IL-27 through STAT1 and STAT3.[2][4][5]
IL-10 Production
IL-10 acts in an anti-inflammatory manner by suppressing inflammatory responses.[6] One way that IL-27 can have an anti-inflammatory response is through the expression of IL-10. IL-27 has been found to be involved in the production of IL-10 by stimulating the various subsets of T cells, especially Tr1 cells. Also involved are the STAT1 and STAT3 transcription factors that bind specifically to the receptor subunits, IL-27ɑ and glycoprotein. IL-27 is able to activate STAT3 signaling, which eventually leads to an increase of IL-10 secretion from Treg cells.[1]
References
- 1 2 3 4 Yoshida, Hiroki; Hunter, Christopher A. (2015-04-10). "The Immunobiology of Interleukin-27". Annual Review of Immunology. 33 (1): 417–443. doi:10.1146/annurev-immunol-032414-112134.
- 1 2 3 4 5 Meka, Rakeshchandra R.; Venkatesha, Shivaprasad H.; Dudics, Steven; Acharya, Bodhraj; Moudgil, Kamal D. "IL-27-induced modulation of autoimmunity and its therapeutic potential". Autoimmunity Reviews. 14 (12): 1131–1141. PMC 4628569
. PMID 26253381. doi:10.1016/j.autrev.2015.08.001. - 1 2 3 Yoshimoto, Takayuki; Chiba, Yukino; Furusawa, Jun-Ichi; Xu, Mingli; Tsunoda, Ren; Higuchi, Kaname; Mizoguchi, Izuru (2015-09-01). "Potential clinical application of interleukin-27 as an antitumor agent". Cancer Science. 106 (9): 1103–1110. ISSN 1349-7006. PMC 4582978 . PMID 26132605. doi:10.1111/cas.12731.
- 1 2 3 Iwasaki, Yukiko; Fujio, Keishi; Okamura, Tomohisa; Yamamoto, Kazuhiko (2015-01-27). "Interleukin-27 in T Cell Immunity". International Journal of Molecular Sciences. 16 (2): 2851–2863. ISSN 1422-0067. PMC 4346869 . PMID 25633106. doi:10.3390/ijms16022851.
- 1 2 3 Aparicio-Siegmund, Samadhi; Garbers, Christoph (2015-10-01). "The biology of interleukin-27 reveals unique pro- and anti-inflammatory functions in immunity". Cytokine & Growth Factor Reviews. 26 (5): 579–586. ISSN 1879-0305. PMID 26195434. doi:10.1016/j.cytogfr.2015.07.008.
- ↑ Iyer, Shankar Subramanian; Cheng, Genhong (2012-01-01). "Role of Interleukin 10 Transcriptional Regulation in Inflammation and Autoimmune Disease". Critical reviews in immunology. 32 (1): 23–63. ISSN 1040-8401. PMC 3410706 . PMID 22428854.