Interleukin-22: A novel T- and NK-cell derived cytokine that regulates the biology of tissue cells
Abstract
Interleukin (IL)-22, discovered in 2000, is a member of the IL-10 family of cytokines. The major sources of IL-22 are activated T1- and NK-cells. IL-22 acts via a heterodimeric receptor complex consisting of IL-22R1 and IL-10R2. Neither resting nor activated immune cells express IL-22R1 or respond to IL-22. In contrast, tissue cells at outer body barriers, i.e. of the skin, kidney, and the digestive and respiratory systems are targets of this cytokine. IL-22 functions by promoting the anti-microbial defense, protecting against damage, and re-organizing non-immune tissues. Furthermore, IL-22 induces acute phase reactants. These findings indicate that IL-22 represents a novel type of immune mediator that, although produced by immune cells, regulates tissue protection and homeostasis.
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In vitro studies suggest that IL-22 signals to epithelial keratinocytes of the skin to promote proliferation and migration and induce AMPs.
“In vitro studies have suggested that IL-22 signals to epithelial keratinocytes of the skin to promote proliferation and migration and inducing AMPs.85,86”
From The Innate Immune System in Acute and Chronic Wounds (2016) · cites this paper as [86]
Cites
Williams, H. C., Leung, D. Y. M., Thestrup‐Pedersen, K., & David, T. J. (2000) · Cited by 4,597 · see citing works
IFN-λs mediate antiviral protection through a distinct class II cytokine receptor complex
Kotenko, S. V., Gallagher, G. E., Baurin, V. V., Lewis-Antes, A., Shen, M., Shah, N. K., Langer, J. A., Sheikh, F. G., Dickensheets, H. L., & Donnelly, R. P. (2002) · Nature Immunology · doi:10.1038/ni875 · Cited by 1,867 · see citing works
IL-28, IL-29 and their class II cytokine receptor IL-28R
Sheppard, P. O., Kindsvogel, W., Xu, W., Henderson, K., Schlutsmeyer, S., Whitmore, T. E., Kuestner, R. E., Garrigues, U., Birks, C., Roraback, J., et al. (2002) · Nature Immunology · doi:10.1038/ni873 · Cited by 1,563 · see citing works
IL-22 Increases the Innate Immunity of Tissues
Wolk, K., Kunz, S., Witte, E., Friedrich, M., Asadullah, K., & Sabat, R. (2004) · Immunity · doi:10.1016/j.immuni.2004.07.007 · Cited by 1,362 · see citing works
Self-citationLeung, D. Y. M., & Bieber, T. R. M. (2003) · The Lancet · doi:10.1016/s0140-6736(03)12193-9 · Cited by 1,149 · see citing works
I nterleukin -10 and R elated C ytokines and R eceptors
Pestka, S., Krause, C. D., Sarkar, D., Walter, M. R., Shi, Y., & Fisher, P. B. (2004) · Annual Review of Immunology · doi:10.1146/annurev.immunol.22.012703.104622 · Cited by 1,097 · see citing works
Wolk, K., Witte, E., Wallace, E., Döcke, W., Kunz, S., Asadullah, K., Volk, H., Sterry, W., & Sabat, R. (2006) · European Journal of Immunology · doi:10.1002/eji.200535503 · Cited by 992 · see citing works
Self-citationBoniface, K., Bernard, F.-X., Garcia, M., Gurney, A. L., Lecron, J.-C., & Morel, F. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.6.3695 · Cited by 864 · see citing works
Radaeva, S., Sun, R., Pan, H., Hong, F., & Gao, B. (2004) · Hepatology · doi:10.1002/hep.20184 · Cited by 638 · see citing works
Cutting Edge: Immune Cells as Sources and Targets of the IL-10 Family Members?
Wolk, K., Kunz, S., Asadullah, K., & Sabat, R. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.11.5397 · Cited by 581 · see citing works
Self-citationMyofibroblasts. II. Intestinal subepithelial myofibroblasts
Powell, D. W., Mifflin, R. C., Valentich, J. D., Crowe, S. E., Saada, J. I., & West, A. B. (1999) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1999.277.2.c183 · Cited by 566 · see citing works
Blumberg, H., Conklin, D., Xu, W., Grossmann, A., Brender, T., Carollo, S., Eagan, M., Foster, D., Haldeman, B. A., Hammond, A., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00187-8 · Cited by 542 · see citing works
Xie, M.-H., Aggarwal, S., Ho, W.-H., Foster, J., Zhang, Z., Stinson, J., Wood, W. I., Goddard, A. D., & Gurney, A. L. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m005304200 · Cited by 541 · see citing works
Dumoutier, L., Louahed, J., & Renauld, J. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.4.1814 · Cited by 500 · see citing works
Jiang, H., Lin, J. J., Su, Z.-Z., Goldstein, N. I., & Fisher, P. B. (1995) · PubMed · Cited by 486 · see citing works
Andoh, A., Zhang, Z., Inatomi, O., Fujino, S., Deguchi, Y., Araki, Y., Tsujikawa, T., Kitoh, K., Kim‐Mitsuyama, S., Takayanagi, A., et al. (2005) · Gastroenterology · doi:10.1053/j.gastro.2005.06.071 · Cited by 480 · see citing works
Lejeune, D., Dumoutier, L., Constantinescu, S. N., Kruijer, W., Schuringa, J. J., & Renauld, J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204204200 · Cited by 478 · see citing works
Dumoutier, L., Leemans, C., Lejeune, D., Kotenko, S. V., & Renauld, J.-C. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.7.3545 · Cited by 405 · see citing works
Identification of the Functional Interleukin-22 (IL-22) Receptor Complex
Kotenko, S. V., Izotova, L. S., Mirochnitchenko, O. V., Esterova, E., Dickensheets, H. L., Donnelly, R. P., & Pestka, S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m007837200 · Cited by 400 · see citing works
Expression of interleukin‐22 in rheumatoid arthritis: Potential role as a proinflammatory cytokine
Ikeuchi, H., Kuroiwa, T., Hiramatsu, N., Kaneko, Y., Hiromura, K., Ueki, K., & Nojima, Y. (2005) · Arthritis & Rheumatism · doi:10.1002/art.20965 · Cited by 399 · see citing works
Kotenko, S. V., Krause, C. D., Izotova, L. S., Pollack, B. P., Wu, W., & Pestka, S. (1997) · The EMBO Journal · doi:10.1093/emboj/16.19.5894 · Cited by 382 · see citing works
Dumoutier, L., Roost, E. V., Colau, D., & Renauld, J. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.170291697 · Cited by 365 · see citing works
The expanded family of class II cytokines that share the IL-10 receptor-2 (IL-10R2) chain
Donnelly, R. P., Sheikh, F., Kotenko, S. V., & Dickensheets, H. (2004) · Journal of Leukocyte Biology · doi:10.1189/jlb.0204117 · Cited by 289 · see citing works
Gallagher, G. E., Dickensheets, H. L., Eskdale, J., Ls, I., Mirochnitchenko, O., Peat, J. E., Vazquez, N., Pestka, S., Donnelly, R. P., & Kotenko, S. V. (2000) · Genes and Immunity · doi:10.1038/sj.gene.6363714 · Cited by 288 · see citing works
Interleukins 19, 20, and 24 Signal through Two Distinct Receptor Complexes
Parrish-Novak, J. E., Xu, W., Brender, T., Yao, L. Y., Jones, C. A., West, J., Brandt, C. S., Jelinek, L., Madden, K., McKernan, P. A., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205114200 · Cited by 268 · see citing works
Kotenko, S. V., Izotova, L. S., Mirochnitchenko, O. V., Esterova, E., Dickensheets, H., Donnelly, R. P., & Pestka, S. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.12.7096 · Cited by 260 · see citing works
Antimicrobial skin peptides and proteins
Schröder, J. ‐., & Harder, J. (2006) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-005-5364-0 · Cited by 252 · see citing works
Dumoutier, L., Lejeune, D., Colau, D., & Renauld, J. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.12.7090 · Cited by 251 · see citing works
Zdanov, A. S., Schalk‐Hihi, C., Gustchina, A., Tsang, M., Weatherbee, J. A., & Wlodawer, A. (1995) · Structure · doi:10.1016/s0969-2126(01)00193-9 · Cited by 235 · see citing works
Knappe, A., Hör, S., Wittmann, S., & Fickenscher, H. (2000) · Journal of Virology · doi:10.1128/jvi.74.8.3881-3887.2000 · Cited by 214 · see citing works
The family of IL-10-related cytokines and their receptors: related, but to what extent?
Kotenko, S. V. (2002) · Cytokine & Growth Factor Reviews · doi:10.1016/s1359-6101(02)00012-6 · Cited by 213 · see citing works
A soluble class II cytokine receptor, IL-22RA2, is a naturally occurring IL-22 antagonist
Xu, W., Presnell, S., Parrish-Novak, J. E., Kindsvogel, W., Jaspers, S., Chen, Z., Dillon, S. R., Gao, Z., Gilbert, T., Madden, K., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.171303198 · Cited by 212 · see citing works
IL-TIF/IL-22: genomic organization and mapping of the human and mouse genes
Dumoutier, L., Roost, E. V., Ameye, G., et al. (2000) · Genes and Immunity · doi:10.1038/sj.gene.6363716 · Cited by 211 · see citing works
Crystal Structure of the IL-10/IL-10R1 Complex Reveals a Shared Receptor Binding Site
Josephson, K., Logsdon, N. J., & Walter, M. R. (2001) · Immunity · doi:10.1016/s1074-7613(01)00169-8 · Cited by 211 · see citing works
The Class II cytokine receptor (CRF2) family: overview and patterns of receptor–ligand interactions
Langer, J. A., Cutrone, E. C., & Kotenko, S. V. (2004) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2003.10.001 · Cited by 193 · see citing works
Pan, H., Hong, F., Radaeva, S., & Gao, B. (2004) · PubMed · Cited by 186 · see citing works
Acinar Cells of the Pancreas Are a Target of Interleukin-22
Aggarwal, S., Xie, M.-H., Maruoka, M., Foster, J., & Gurney, A. L. (2001) · Journal of Interferon & Cytokine Research · doi:10.1089/107999001317205178 · Cited by 170 · see citing works
Oral, H. B., Kotenko, S. V., Yılmaz, M., Mani, O., Zumkehr, J., Blaser, K., Akdiş, C. A., & Akdiş, M. (2005) · European Journal of Immunology · doi:10.1002/eji.200425523 · Cited by 141 · see citing works
Crystal Structure of Interleukin 10 Reveals an Interferon .gamma.-like Fold
Walter, M. R., & Nagabhushan, T. L. (1995) · Biochemistry · doi:10.1021/bi00038a004 · Cited by 135 · see citing works
Crystal Structure of Recombinant Human Interleukin-22
Nagem, R. A. P., Colau, D., Dumoutier, L., Renauld, J., Ogata, C. M., & Polikarpov, I. (2002) · Structure · doi:10.1016/s0969-2126(02)00797-9 · Cited by 130 · see citing works
Whittington (2004) · doi:10.1165/rcmb.2003-0285oc · Cited by 130 · see citing works
Is there an interaction between interleukin-10 and interleukin-22?
Wolk, K., Witte, E., Reineke, U., Witte, K., Friedrich, M., Sterry, W., Asadullah, K., Volk, H., & Sabat, R. (2004) · Genes and Immunity · doi:10.1038/sj.gene.6364144 · Cited by 106 · see citing works
Self-citationComparison of Interleukin-22 and Interleukin-10 Soluble Receptor Complexes
Logsdon, N. J., Jones, B. C., Josephson, K., Cook, J., & Walter, M. R. (2002) · Journal of Interferon & Cytokine Research · doi:10.1089/10799900260442520 · Cited by 99 · see citing works
Therapeutic potential of follistatin for colonic inflammation in mice
Dohi, T., Ejima, C., Kato, R., Kawamura, Y. I., Kawashima, R., Mizutani, N., Tabuchi, Y., & Kojima, I. (2005) · Gastroenterology · doi:10.1053/j.gastro.2004.11.063 · Cited by 95 · see citing works
Activin A: a novel player and inflammatory marker in inflammatory bowel disease?
Hübner, G., Brauchle, M. A., Gregor, M., & Werner, S. (1997) · PubMed · Cited by 94 · see citing works
On the protein-protein diffusional encounter complex
Gabdoulline, R. R., & Wade, R. C. (1999) · Journal of Molecular Recognition · doi:10.1002/(sici)1099-1352(199907/08)12:4 · Cited by 88 · see citing works
Growth factors and the gastrointestinal tract
Murphy, M. S. (1998) · Nutrition · doi:10.1016/s0899-9007(98)00081-1 · Cited by 88 · see citing works
Crystal Structure of Interleukin-19 Defines a New Subfamily of Helical Cytokines
Chang, C., Magracheva, E., Kozlov, S. V., Fong, S., Tobin, G. J., Kotenko, S. V., Wlodawer, A., & Zdanov, A. S. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m208602200 · Cited by 82 · see citing works
Logsdon, N. J., Jones, B. C., Allman, J. C., Izotova, L. S., Schwartz, B., Pestka, S., & Walter, M. R. (2004) · Journal of Molecular Biology · doi:10.1016/j.jmb.2004.07.069 · Cited by 76 · see citing works
Cloning and characterization of mouse IL-22 binding protein
Wei, C.-C., Ho, T.-W., Liang, W.-G., Chen, G.-Y., & Chang, M. (2003) · Genes and Immunity · doi:10.1038/sj.gene.6363947 · Cited by 68 · see citing works
Temporal associations between interleukin 22 and the extracellular domains of IL-22R and IL-10R2
Li, J., Tomkinson, K. N., Tan, X., Wu, P. W., Yan, G., Spaulding, V., Deng, B., Annis-Freeman, B., Heveron, K., Zollner, R., et al. (2004) · International Immunopharmacology · doi:10.1016/j.intimp.2004.01.010 · Cited by 66 · see citing works
A novel, soluble homologue of the human IL-10 receptor with preferential expression in placenta
Grünberg, B. H., Schoenemeyer, A., Weiss, B., Toschi, L., Kunz, S., Wolk, K., Asadullah, K., & Sabat, R. (2001) · Genes and Immunity · doi:10.1038/sj.gene.6363786 · Cited by 63 · see citing works
Self-citationMapping of the interleukin‐10/interleukin‐10 receptor combining site
Reineke, U., Sabat, R., Volk, H., & Schneider‐Mergener, J. (1998) · Protein Science · doi:10.1002/pro.5560070412 · Cited by 61 · see citing works
Self-citationCloning of murine IL-22 receptor alpha 2 and comparison with its human counterpart
Weiss, B., Wolk, K., Grünberg, B. H., Volk, H., Sterry, W., Asadullah, K., & Sabat, R. (2004) · Genes and Immunity · doi:10.1038/sj.gene.6364104 · Cited by 57 · see citing works
Self-citationIL-10 and its homologs: important immune mediators and emerging immunotherapeutic agents
Volk, H., Asadullah, K., Gallagher, G. E., et al. (2001) · Trends in Immunology · doi:10.1016/s1471-4906(01)01985-8 · Cited by 52 · see citing works
Structure of insect-cell-derived IL-22
Xu, T., Logsdon, N. J., & Walter, M. R. (2005) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444905009601 · Cited by 51 · see citing works
Salazar, A., Pintó, X., & Mañá, J. (2001) · European Journal of Clinical Investigation · doi:10.1046/j.1365-2362.2001.00913.x · Cited by 44 · see citing works
Lécart, S. (2002) · International Immunology · doi:10.1093/intimm/dxf096 · Cited by 44 · see citing works
Kalabis, J., Patterson, M. J., Enders, G. H., et al. (2003) · The FASEB Journal · doi:10.1096/fj.02-0852fje · Cited by 34 · see citing works
Interleukin‐11: Its Biology and Prospects for Clinical Use
Grosfeld, J. L., Du, X., & Williams, D. A. (1999) · Journal of Parenteral and Enteral Nutrition · doi:10.1177/014860719902300517 · Cited by 25 · see citing works
Nagakawa, H., Shimozato, O., Yu, L., et al. (2004) · Scandinavian Journal of Immunology · doi:10.1111/j.0300-9475.2004.01504.x · Cited by 22 · see citing works
Genomic structure and inducible expression of the IL-22 receptor α chain in mice
Tachiiri, A., Imamura, R., Wang, Y., Fukui, M., Umemura, M., & Suda, T. (2003) · Genes and Immunity · doi:10.1038/sj.gene.6363934 · Cited by 8 · see citing works
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Belkaid, Y., & Hand, T. W. (2014) · Cell · doi:10.1016/j.cell.2014.03.011 · Cited by 5,385 · see citing works
Korn, T., Bettelli, E., Oukka, M., & Kuchroo, V. K. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132710 · Cited by 4,873 · see citing works
Romani, L. (2011) · Nature Reviews Immunology · doi:10.1038/nri2939 · Cited by 1,793 · see citing works
Impaired TH17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome
Milner, J. D., Brenchley, J. M., Laurence, A., Freeman, A. F., Hill, B. J., Elias, K. M., Kanno, Y., Spalding, C., Elloumi, H. Z., Paulson, M. L., et al. (2008) · Nature · doi:10.1038/nature06764 · Cited by 1,157 · see citing works
Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells
Duhen, T., Geiger, R., Jarrossay, D., Lanzavecchia, A., & Sallusto, F. (2009) · Nature Immunology · doi:10.1038/ni.1767 · Cited by 1,079 · see citing works
Trifari, S., Kaplan, C. D., Tran, E. H., Crellin, N. K., & Spits, H. (2009) · Nature Immunology · doi:10.1038/ni.1770 · Cited by 1,021 · see citing works
Influenza A inhibits Th17-mediated host defense against bacterial pneumonia in mice.
Kudva, A., Scheller, E. V., Robinson, K. M., Crowe, C. R., Choi, S. M., Slight, S. R., Khader, S. A., Dubin, P. J., Enelow, R. I., Kolls, J. K., et al. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1002194 · Cited by 346 · see citing works
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MacLeod, A. S., & Mansbridge, J. N. (2016) · Advances in Wound Care · doi:10.1089/wound.2014.0608 · Cited by 289 · see citing works
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Dhiman, R., Venkatasubramanian, S., Paidipally, P., Barnes, P. F., Tvinnereim, A., & Vankayalapati, R. (2014) · The Journal of Infectious Diseases · doi:10.1093/infdis/jit495 · Cited by 68 · see citing works
Ziesché, E., Scheiermann, P., Bachmann, M., Sadik, C. D., Hofstetter, C., Zwissler, B., Pfeilschifter, J., & Mühl, H. (2009) · Clinical and Experimental Immunology · doi:10.1111/j.1365-2249.2009.03969.x · Cited by 40 · see citing works
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Alabbas, S. Y., Begun, J., Florin, T. H., & Oancea, I. (2018) · Clinical & Translational Immunology · doi:10.1002/cti2.1017 · Cited by 37 · see citing works
Naglik, J. R. (2014) · New Journal of Science · doi:10.1155/2014/390241 · Cited by 29 · see citing works
- Authors
- Wolk, K., & Sabat, R.
- Affiliations
- Stiftung Charité (DE)
- Corresponding author
- Sabat, Robert
- Venue
- Cytokine & Growth Factor Reviews
- Publisher
- Elsevier BV
- Published
- 2006-10
- Volume
- 17
- Issue
- 5
- Pages
- 367-380
- ISSN
- 1359-6101 (ISSN-L)
- OpenAlex
- W2038539820
- Cited by
- 303
- References
- 62
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 5 · 2023: 5 · 2022: 10 · 2021: 10 · 2020: 9 · 2019: 10 · 2018: 14 · 2017: 12 · 2016: 14 · 2015: 8 · 2014: 24 · 2013: 19 · 2012: 23
- FWCI
- 2.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cytokine & Growth Factor Reviews (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Keywords
- IL-22, IL-10 family cytokines, IL-10R2, T cells, natural killer cells, tissue protection, tissue homeostasis, antimicrobial defense, acute phase proteins, skin, kidney, mucosal immunity
- MeSH terms
- Interleukin-22, Humans, Interleukins, Killer Cells, Natural, T-Lymphocytes, Signal Transduction, Receptors, Interleukin, Interleukin-10 Receptor beta Subunit
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