IL-10 family

The IL-10 family is a family of interleukins. They are helical cytokines categorized based on their specific similarities and can be classified as class 2 cytokines.[1]

In addition to IL-10, it includes IL-19, IL-20, IL-22, IL-24 and IL-26.[2]

Some sources also include the type III interferons IL-28 and IL-29.[3]

Classification

It is well-accepted interferons are class 2 cytokines just like the IL-10 family members, but their precise relationship is unknown due to difficulties in rooting the tree.

Phylogenies
Typical midpoint rooting[4] Interleukins as outgroup[5]

Type IV IFN

Type I IFN

Type II IFN

Type III IFN

IL-22

IL-20

IL-10

Type I IFN

Type IV IFN

Type III IFN

Jawless IFN

Type II IFN

Lancelet IFN

IL-22

IL-20

IL-19

IL-24

IL-26

IL-10

The receptors and signaling functions are:[6]

CytokinesReceptor αReceptor βStat moleculeAdditional partners
IL-10IL-10RAIL-10RBStat3, Stat1, Stat5
IL-19/20/24IL-20RAIL-20RBStat3, Stat5
IL-20/24IL-22RIL-20RBStat3, Stat5
IL-22IL-22RIL-10RBStat3, Stat1, Stat5IL-22BP (antagonist)
IL-26IL-20RAIL-10RBStat3, Stat1
IL-28A/28B/29IL-28RIL-10RBStat1, Stat2


Based on the functions of the cytokine, the IL-10 family is traditionally separated into three subfamily groups:

  • IL-10 (only member of its subfamily) selects the innate and adaptive immune response and can prevent the function to reduce tissue damage.[6]
  • The IL-20 subfamily (IL-19, IL-20, IL-22, IL-24, IL-26) of cytokine works on tissues in the stroma and epithelial cells to bring out the mechanism of innate defense that manages the attack of extracellular pathogens.[6]
  • The IL-28 subfamily of cytokine are type III interferon (IFN) family.[6] This subfamily share intersecting biology and signaling pathways with type I IFN family cytokines but the difference is that the type III INF family cytokines prefer to target the tissues of the epithelial cell.[6]

Biological activity

The IL-10 family is one of the important types of cytokines, that can stop the inflammation. In general. these cytokines have a helical structure of homodimers.[7] The difference that the members of IL-10 family have between each other is that they have various receptor-binding residues, which help with interaction with specific cytokine receptors.[8] The features of the IL-10 family consists of their genomic structure being similar, their primary and secondary protein structures being similar, their a clustering of encoding genes, and their utilization the similar receptor complexes.[1]

IL-10

Interleukin 10 is produced by regulatory T lymphocytes, B cells, and monocytes. It is a homodimer that functions through the IL-10R1 and IL-10R2 receptor complexes, activating such kinases as Janus kinase and tyrosine kinase 2.[9] IL-10R2 receptor is presented in most cells, when IL-10R1 receptor is IL-10 is also an inhibitor of expressions of CD80 and CD86 by dendritic cells (DC) and antigen-presenting cells (APC),[9] and of T cells, decreasing their cytokine production, therefore, controlling their activation. IL-10 plays a big role in regulating allergies by inhibiting cytokines responsible for allergic inflammation.

IL-19

Interleukin 19 is produced mainly in monocytes, and can be found in big concentrations in patients with allergic disorders and psoriasis. IL-19 plays a big role in the CNS by regulating the inflammation process through a delayed production of it.[10]

IL-20

IL-20 - induces cheratin proliferation and Stat-3 signal transduction pathway;[10] is expressed in the CNS, myeloid cells, and keratinocytes. When IL-20 is inhibited in the CNS can stop such inflammations as acute ischemic brain injury.[10][9]

IL-22

IL-22 mediates inflammation and binds class II cytokine receptor heterodimers IL-22 RA1/CRF2-4;[11] is involved in immuno-regulatory responses

IL-24

IL-24 produced by activated monocytes and T-cells.[12]

IL-26

IL-26 is a newly discovered cytokine produced by memory T cells and monocytes. IL-26 assist with the process of human T cell transformation after their infections.[12]

References

  1. 1 2 Sabat, Robert (2010-10-01). "IL-10 family of cytokines". Cytokine & Growth Factor Reviews. 21 (5): 315–324. doi:10.1016/j.cytogfr.2010.11.001. ISSN 1359-6101. PMID 21112807.
  2. ↑ Conti P, Kempuraj D, Frydas S, et al. (September 2003). "IL-10 subfamily members: IL-19, IL-20, IL-22, IL-24 and IL-26". Immunol. Lett. 88 (3): 171–4. doi:10.1016/S0165-2478(03)00087-7. PMID 12941475.
  3. ↑ Commins S, Steinke JW, Borish L (May 2008). "The extended IL-10 superfamily: IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, IL-28, and IL-29". J. Allergy Clin. Immunol. 121 (5): 1108–11. doi:10.1016/j.jaci.2008.02.026. PMID 18405958.
  4. ↑ Chen, Shan Nan; Gan, Zhen; Hou, Jing; Yang, Yue Cong; Huang, Lin; Huang, Bei; Wang, Su; Nie, Pin (22 February 2022). "Identification and establishment of type IV interferon and the characterization of interferon-υ including its class II cytokine receptors IFN-υR1 and IL-10R2". Nature Communications. 13 (1) 999. Bibcode:2022NatCo..13..999C. doi:10.1038/s41467-022-28645-6. PMC 8863823. PMID 35194032.
  5. ↑ Wang, Xinli; Wang, Qinghuan; Xie, Anni; Deng, Lisi; Huang, Ziwen; Zhao, Yiming; Cao, Yange; Fu, Rong; Huo, Weicong; Chen, Yanhong; Li, Guang; Xu, Anlong; Yuan, Shaochun (2026-06-03). "Tracing the Evolutionary Origin of Interferon to Basal Chordates and Unveiling Its Antiviral Functionality in Jawless Vertebrates". bioRxiv 10.64898/2026.05.30.728932.
  6. 1 2 3 4 5 Ouyang, Wenjun; O’Garra, Anne (2019-04-16). "IL-10 Family Cytokines IL-10 and IL-22: from Basic Science to Clinical Translation". Immunity. 50 (4): 871–891. doi:10.1016/j.immuni.2019.03.020. ISSN 1074-7613. PMID 30995504. S2CID 122350808.
  7. ↑ Fickenscher, Helmut; Hör, Simon; Küpers, Heide; Knappe, Andrea; Wittmann, Sabine; Sticht, Heinrich (2002-02-01). "The interleukin-10 family of cytokines". Trends in Immunology. 23 (2): 89–96. doi:10.1016/S1471-4906(01)02149-4. ISSN 1471-4906. PMID 11929132.
  8. ↑ Trivella, Daniela Barretto Barbosa; Ferreira-Júnior, José Ribamar; Dumoutier, Laure; Renauld, Jean-Christophe; Polikarpov, Igor (September 2010). "Structure and function of interleukin-22 and other members of the interleukin-10 family". Cellular and Molecular Life Sciences. 67 (17): 2909–2935. doi:10.1007/s00018-010-0380-0. ISSN 1420-682X. PMC 11115847. PMID 20454917. S2CID 10926488.
  9. 1 2 3 Commins, Scott; Steinke, John W.; Borish, Larry (2008-05-01). "The extended IL-10 superfamily: IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, IL-28, and IL-29". Journal of Allergy and Clinical Immunology. 121 (5): 1108–1111. doi:10.1016/j.jaci.2008.02.026. ISSN 0091-6749. PMID 18405958.
  10. 1 2 3 Burmeister, Amanda R.; Marriott, Ian (2018). "The Interleukin-10 Family of Cytokines and Their Role in the CNS". Frontiers in Cellular Neuroscience. 12 458. doi:10.3389/fncel.2018.00458. ISSN 1662-5102. PMC 6277801. PMID 30542269.
  11. ↑ Lerner, Ulf H. (2020-01-01), "Role of Interleukins on Physiological and Pathological Bone Resorption and Bone Formation: Effects by Cytokines in The IL-6 and IL-10 Families", in Zaidi, Mone (ed.), Encyclopedia of Bone Biology, Oxford: Academic Press, pp. 67–87, ISBN 978-0-12-814082-6, retrieved 2020-11-24
  12. 1 2 Scrivo, R.; Conigliaro, P.; Riccieri, V.; Di Franco, M.; Alessandri, C.; Spadaro, A.; Perricone, R.; Valesini, G. (2015). "Distribution of interleukin-10 family cytokines in serum and synovial fluid of patients with inflammatory arthritis reveals different contribution to systemic and joint inflammation". Clinical and Experimental Immunology. 179 (2): 300–308. doi:10.1111/cei.12449. PMC 4298407. PMID 25178435.
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