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]
Autophagy inhibition
IL-27 plays a crucial role in mycobacterium tuberculosis infection. IL-27 inhibits IFN-gamma induced autophagy by activating PI3K/Akt/mTOR pathway and up-regulation of an anti apoptotic protein Mcl-1, in Mycobacterium tuberculosis H37Rv strain infected human macrophages.[7]
References
- ^ a b c d 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.
- ^ a b c d e 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. doi:10.1016/j.autrev.2015.08.001. PMC 4628569. PMID 26253381.
- ^ a b c 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. doi:10.1111/cas.12731. ISSN 1349-7006. PMC 4582978. PMID 26132605.
- ^ a b c 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. doi:10.3390/ijms16022851. ISSN 1422-0067. PMC 4346869. PMID 25633106.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ a b c 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. doi:10.1016/j.cytogfr.2015.07.008. ISSN 1879-0305. PMID 26195434.
- ^ 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.
- ^ Sharma, Gaurav; Dutta, Rajesh Kumar; Khan, Mohammad Aslam; Ishaq, Mohammad; Sharma, Kapil; Malhotra, Himanshu; Majumdar, Sekhar (2014-10). "IL-27 inhibits IFN-γ induced autophagy by concomitant induction of JAK/PI3 K/Akt/mTOR cascade and up-regulation of Mcl-1 in Mycobacterium tuberculosis H37Rv infected macrophages". The International Journal of Biochemistry & Cell Biology. 55: 335–347. doi:10.1016/j.biocel.2014.08.022. ISSN 1357-2725.
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