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Cytokines IL-17 and IL-22 in the host response to infection
Open accessAbstract
Cytokines IL-17 and IL-22 play pivotal roles in host defense against microbes and in the development of chronic inflammatory diseases. These cytokines are produced by cells that are often located in epithelial barriers, including subsets of T cells and innate lymphoid cells. In general, IL-17 and IL-22 can be characterized as important cytokines in the rapid response to infectious agents, both by recruiting neutrophils and by inducing the production of antimicrobial peptides. Although each cytokine induces an innate immune response in epithelial cells, their functional spectra are generally distinct: IL-17 mainly induces an inflammatory tissue response and is involved in the pathogenesis of several autoimmune diseases, whereas IL-22 is largely protective and regenerative. In this review, we compare IL-17 and IL-22, describing overlaps and differences in their cellular sources as well as their regulation, signaling, biological functions and roles during disease, with a focus on the contribution of these cytokines to the gut mucosal barrier during bacterial infection.
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“pointing to a broad evolutionary conservation of all individual family members in the rapid response to infectious agents112.”
From Chromosomal-level reference genome assembly of muskox (Ovibos moschatus) from Banks Island in the Canadian Arctic, a resource for conservation genomics (2024) · cites this paper as [112]
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IL-22: There Is a Gap in Our Knowledge
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Interleukins (Cytokines) as Biomarkers in Colorectal Cancer: Progression, Detection, and Monitoring
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“PRRs are constantly exposed to PAMPs, also during gut homeostasis, in the absence of any infection (66).”
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“Given the role of IL-17/ IL-22-producing lymphocytes in contributing to the maintenance of intestinal epithelial barrier integrity (36), we investigated the relationship between IL-17/IL-22 cytokine effector functions of classical and innate Th17-type cells in blood and gut mucosa and”
BackgroundResponse to Vaccines in Patients with Immune-Mediated Inflammatory Diseases: A Narrative Review
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“IL-17A is a proinflammatory cytokine produced by Th17 cells which induces the release of many cytokines (such as IL-6, G-CSF, GM-CSF, IL-1β, TGF-β, TNF-α) and chemokines (including IL-8, GRO-α and MCP-1) [39,40], with the final goal of increasing inflammation, the generation of granulocytes by bone marrow and attracti…”
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BackgroundInfluentialThe Role of Group 3 Innate Lymphoid Cells in Lung Infection and Immunity
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“Early production of IL-17 and IL-22 is a critical factor in neutrophil recruitment as well as in host defense against pathogens via the effect on the induction of antimicrobial peptide expression (Ye et al., 2001; Liang et al., 2006; Aujla et al., 2008; Bayes et al., 2016a; Trevejo-Nunez et al., 2016; Valeri and Raffa…”
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“…ZIKV titers suggesting that difference in titers among different VMBs could be due to a variety of factors, including but not limited to: differences in minor organisms within the microbiome, differences in the community profile, or bacteriophages (van de Wijgert et al., 2014; Malki et al., 2016).”
BackgroundDietary cysteine enhances intestinal stemness via CD8+ T cell-derived IL-22
Chi, F., Zhang, Q., Shay, J. E. S., Han, S., ten Hoeve, J., Yuan, Y., Yang, Z., Shin, H., Block, S., Solanki, S. A., et al. (2025) · Nature · doi:10.1038/s41586-025-09589-5 · Cited by 23
Up-regulated expression of substance P in CD8+ T cells and NK1R on monocytes of atopic dermatitis
Zhang, Z., Zheng, W., Xie, H., Chai, R., Wang, J., Zhang, H., & He, S. (2017) · Journal of Translational Medicine · doi:10.1186/s12967-017-1196-6 · Cited by 21
“IL-13 is a key Th2 cytokine involved in atopic disease, while IFN-γ and IL-22 play pivotal roles in host defence against microbes and in the development of chronic inflammatory diseases [6].”
Zhou, X., Johnson, J. S., Spakowicz, D. J., Zhou, W., Zhou, Y., Sodergren, E. J., Snyder, M. P., & Weinstock, G. M. (2020) · Diabetes · doi:10.2337/db19-0592 · Cited by 21
“While Th17 cells are a major source of IL-17 and IL-22 (16,19), other cell types also produce these cytokines (20) and may be important in this process.”
BackgroundTofacitinib for the treatment of active ankylosing spondylitis in adults
Mohanakrishnan, R., Beier, S., & Deodhar, A. (2022) · Expert Review of Clinical Immunology · doi:10.1080/1744666x.2022.2038134 · Cited by 21
“site musculoskeletal involvement and ‘spill-over’ of proinflammatory cytokines such as IL-23, IL-17, IL-22 in systemic circulation has been implicated as a potential mechanism [11,12].”
BackgroundCombinatorial actions of IL-22 and IL-17 drive optimal immunity to oral candidiasis through SPRRs
Aggor, F. E. Y., Bertolini, M., Coleman, B. M., Taylor, T. C., Ponde, N. O., & Gaffen, S. L. (2024) · PLoS Pathogens · doi:10.1371/journal.ppat.1012302 · Cited by 20
Holloman, B. L., Cannon, A. S., Wilson, K. M., Nagarkatti, P. S., & Nagarkatti, M. (2023) · mBio · doi:10.1128/mbio.03137-22 · Cited by 20
Park, J., Nguyen, T. M. N., Park, H.-A., Nguyen, M. T. T., Lee, N.-Y., Ban, S.-Y., Park, K.-B., Lee, C., Kim, J., & Park, J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241612803 · Cited by 20
“Even though these cytokines are important for modulation of the immune response for protection of the host, excessive production of pro-inflammatory cytokines may cause chronic inflammation and negative consequences [5].”
BackgroundInflammatory pathways of Toxoplasma gondii infection in pregnancy
Moghaddami, R., Mahdipour, M., & Ahmadpour, E. (2024) · Travel Medicine and Infectious Disease · doi:10.1016/j.tmaid.2024.102760 · Cited by 19
Pickering, H. C., Palmer, C. D., Houghton, J., Makalo, P., Joof, H., Derrick, T. R., Gonçalves, A., Mabey, D. C. W., Bailey, R. L., Burton, M. J., et al. (2019) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2019.00297 · Cited by 19
Kelly, A. M., & McLoughlin, R. M. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00767 · Cited by 18
Biological Therapy for Inflammatory Bowel Disease
Leal, R. F., & Torriani, T. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.83074 · Cited by 18
Macrolide Inspired Macrocycles as Modulators of the IL-17A/IL-17RA Interaction
Koštrun, S., Fajdetić, A., Pešić, D., Brajša, K., Mihaljević, V. B., Jelić, D., Grba, A. P., Elenkov, I., Rupčić, R., Kapić, S., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c00327 · Cited by 21
Activation of mucosal immunity as a novel therapeutic strategy for combating brucellosis
Pascual, D. W., Goodwin, Z. I., Bhagyaraj, E., Hoffman, C. A., & Yang, X. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.1018165 · Cited by 18
“The stimulation of IL-22 is associated with protection of the mucosal epithelium by enhancing the epithelial barrier and increasing defensins production (Valeri and Raffatellu, 2016), and is responsible for stimulation of the heme scavenger, hemopexin, to sequester iron from bacteria (Sakamoto et al.”
BackgroundPhysiological roles of human interleukin‐17 family
Liu, Y., Ouyang, Y., You, W., Liu, W., Cheng, Y., Mai, X., & Shen, Z. (2023) · Experimental Dermatology · doi:10.1111/exd.14964 · Cited by 22
Wu, G., Wang, R., Wang, Y., Sun, S., Chen, J., & Zhang, Q. (2025) · Foods · doi:10.3390/foods14223836 · Cited by 17
Evaluation of two different vaccine platforms for immunization against melioidosis and glanders
Biryukov, S. S., Cote, C. K., Klimko, C. P., Dankmeyer, J. L., Rill, N. O., Shoe, J. L., Hunter, M., Shamsuddin, Z., Vélez, I. D., Hedrick, Z. M., et al. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.965518 · Cited by 17
“Thus, the more controlled cytokine production in the 668 1ilvI- and Conjugate + Hcp1-vaccinated groups, together with enhanced production of cytokines suppressing bacterial dissemination and promoting lung epithelial integrity such as IL-22 and IL-17A (Valeri and Raffatellu, 2016; Alcorn, 2020), were correlated with p…”
BackgroundInfluentialQiu, H., Liu, J., Wu, Q., Ong, H. H., Zhang, Y., Huang, X., Tian, Y., Zheng, R., Deng, H., Wang, W., et al. (2024) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2024.07.006 · Cited by 19
Salerno-Gonçalves, R., Galen, J. E., Levine, M. M., Fasano, A., & Sztein, M. B. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02543 · Cited by 17
Transition metals and host-microbe interactions in the inflamed intestine
Zhu, W., Spiga, L., & Winter, S. (2019) · BioMetals · doi:10.1007/s10534-019-00182-8 · Cited by 17
Malaria-induced bacteremia as a consequence of multiple parasite survival strategies
Donnelly, E. L., de Water, J. V., & Luckhart, S. (2021) · Current Research in Microbial Sciences · doi:10.1016/j.crmicr.2021.100036 · Cited by 19
Mallela, L. S., Sharma, P., Rao, T. S. R. B., & Roy, S. (2021) · Cellular Microbiology · doi:10.1111/cmi.13367 · Cited by 17
“1, γδT cells and type 3 innate lymphoid cells (Valeri & Raffatellu, 2016).”
BackgroundSultan, R. H., Abdallah, M., Ali, T. M., Ahmed, A. E., Assal, H. H., Elesawy, B. H., & Ahmed, O. M. (2022) · Vaccines · doi:10.3390/vaccines10071045 · Cited by 17
“IL-17 is a pro-inflammatory cytokine and plays a pivotal role in both host defense mechanisms against infection and in immune regulation [42].”
BackgroundRobust microbe immune recognition in the intestinal mucosa
Schären, O. P., & Hapfelmeier, S. (2021) · Genes and Immunity · doi:10.1038/s41435-021-00131-x · Cited by 19
“pathogen is generally PRR-signaling dependent [52].”
Ismail, M. B., Åkefeldt, S. O., Lourda, M., Gavhed, D., Aricò, M., Henter, J., Delprat, C., & Valentin, H. (2019) · Cytokine · doi:10.1016/j.cyto.2019.154877 · Cited by 16
Mostafa, G. A., Ibrahim, H. M., Shehab, A. A. S., Magdy, S. M., Soliman, N. A., & El-Sherif, D. F. (2022) · Cytokine · doi:10.1016/j.cyto.2022.155870 · Cited by 15
GPR120 promotes neutrophil control of intestinal bacterial infection
Zhou, Z., Yang, W., Yu, T., Yu, Y., Zhao, X., Yu, Y., Gu, C.-C., Bilotta, A. J., Yao, S., Zhao, Q., et al. (2023) · Gut Microbes · doi:10.1080/19490976.2023.2190311 · Cited by 15
“…IL-17A and IL-22, which promote intestinal production of antimicrobial peptides to inhibit bacterial growth and suppress intestinal inflammation 28,29 , as well as TGF-β, which induces intestinal epithelial cell production of amphiregulin to promote intestinal epithelial barrier function 30 .”
BackgroundBitter Taste Receptors in Bacterial Infections and Innate Immunity
Rudolph, E., Dychtenberg, H., Pozniak, A., & Pundir, P. (2025) · Immunity Inflammation and Disease · doi:10.1002/iid3.70232 · Cited by 13
Nitric oxide-modulating biomaterials for therapeutic Immunoengineering
Boo, Y., Choi, S., Kim, J., & Kim, W. J. (2025) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2025.115718 · Cited by 16
Enteric tuft cell inflammasome activation drives NKp46+ILC3 IL22 via PGD2 and inhibits Salmonella
Churchill, M. J., Pandeya, A., Bauer, R., Christopher, T., Krug, S., Honodel, R., Smita, S., Warner, L. M., Mooney, B., Gibson, A. R., et al. (2025) · The Journal of Experimental Medicine · doi:10.1084/jem.20230803 · Cited by 14
Memon, M. A., Naqvi, M. A., Xin, H., Meng, L., Hasan, M. W., Haseeb, M., Lakho, S. A., Aimulajiang, K., Bu, Y., Xu, L., et al. (2020) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0008218 · Cited by 14
“Japonicuminfected mouse liver is limited and related to the powerful function of IL-9 in recruiting inflammatory cells [51].”
BackgroundInnate lymphoid cells in the spotlight: from biomarkers to blueprint for innovative immunotherapy
Kuo, I.-C., Brassard, J., Zandstra, P. W., & McNagny, K. M. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1655730 · Cited by 13
Innovative engineering approaches to model host-microbiome interactions in vitro
Azamar, K. M. M., Sudi, S. D., Mohammadalizadeh, Z., Coffin, C., Parker, I., & Porras, A. M. (2025) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2025.115677 · Cited by 13
Vaccine induced mucosal and systemic memory NK/ILCs elicit decreased risk of SIV/SHIV acquisition
Rahman, M. A., de Castro, I. S., Schifanella, L., Bissa, M., & Franchini, G. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1441793 · Cited by 13
Impact of Th-17 Cytokines on the Regulation of Transporters in Human Placental Explants
Mirdamadi, K., Kwok, J., Nevo, O., Berger, H. M., & Piquette‐Miller, M. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13060881 · Cited by 13
“For example, IL-17A and IL-22 are believed to act in concert in autoimmune pathogenesis and IL-17 has been shown to act synergistically with TNF-α, in the induction of IL-6 in rheumatoid arthritis [44,45].”
BackgroundHappel, A., Gasper, M. A., Balle, C., Konstantinus, I. N., Gamieldien, H., Dabee, S., Gill, K., Bekker, L., Passmore, J.-A. S., & Jaspan, H. B. (2022) · Microbiology Spectrum · doi:10.1128/spectrum.01626-21 · Cited by 12
“Both of these cytokines have been shown to be produced by a range of mucosal immune cells, including various innate lymphoid cells, such as natural killer (NK), NK T, or lymphoid tissue-inducer cells, activated CD41 and CD81 T cells, mucosa-associated invariant T cells, gamma delta T cells, and Th22 and Th17 cells (16…”
BackgroundBrackman, L. C., Dixon, B. R. E. A., Bernard, M., Revetta, F. L., Cowell, R. P., Meenderink, L. M., Washington, M. K., Piazuelo, M. B., & Algood, H. M. S. (2023) · Infection and Immunity · doi:10.1128/iai.00292-23 · Cited by 12
“Th17 responses are key for the control of extracellular pathogens including extracellular bacteria and pathogenic yeasts (19, 20).”
BackgroundZhao, J., Yao, C., Qin, Y., Zhu, H., Guo, H., Ji, B., Li, X., Sun, N., Li, R., Wu, Y., et al. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-06500-4 · Cited by 13
“IL-22 harbors more potent in AMPs induction [28].”
Allergic fungal rhinosinusitis linked to other hyper-IgE syndromes through defective TH17 responses
Sun, H., Knight, J. M., Li, Y.-D., Ashoori, F., Citardi, M. J., Yao, W. C., Corry, D. B., & Luong, A. (2024) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2024.06.022 · Cited by 12
Metadata
- Authors
- Valeri, M., & Raffatellu, M.
- Affiliations
- University of California, Irvine (US)
- Corresponding author
- Raffatellu, Manuela
- ORCID
- Raffatellu, Manuela
- Venue
- Pathogens and Disease
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-12
- Volume
- 74
- Issue
- 9
- Pages
- ftw111
- ISSN
- 2049-632X (ISSN-L)
- PMC
- PMC5975231
- OpenAlex
- W2557937803
- Cited by
- 202
- References
- 242
- Citations by year
- 2026: 16 · 2025: 34 · 2024: 22 · 2023: 20 · 2022: 19 · 2021: 29 · 2020: 26 · 2019: 26 · 2018: 4 · 2017: 6
- FWCI
- 1.16
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Pathogens and Disease (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Burroughs Wellcome Fund
- National Institute of Allergy and Infectious Diseases (R01AI114625, R56AI114625, R21AI121928, R01AI126277, R21AI105374, R37AI126277)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK058057)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Keywords
- IL-17, IL-22, host defense against infection, innate immunity, epithelial barrier function, gut mucosal barrier, bacterial infection, neutrophil recruitment, antimicrobial peptides, innate lymphoid cells, T cells, cytokine signaling, autoimmune disease, chronic inflammation, tissue regeneration
- MeSH terms
- Interleukin-22, Animals, Enterocolitis, Humans, Infections, Interleukins, Cytokines, Interleukin-17, Host-Pathogen Interactions, Disease Resistance
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