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IL-22–producing “T22” T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17–producing TH17 T cells
Open accessAbstract
Background Psoriasis and atopic dermatitis (AD) are common inflammatory skin diseases. An upregulated TH17/IL-23 pathway was demonstrated in psoriasis. Although potential involvement of TH17 T cells in AD was suggested during acute disease, the role of these cells in chronic AD remains unclear.Objective To examine differences in IL-23/TH17 signal between these diseases and establish relative frequencies of T-cell subsets in AD.Methods Skin biopsies and peripheral blood were collected from patients with chronic AD (n = 12) and psoriasis (n = 13). Relative frequencies of CD4+ and CD8+ T-cell subsets within these 2 compartments were examined by intracellular cytokine staining and flow cytometry.Results In peripheral blood, no significant difference was found in percentages of different T-cell subsets between these diseases. In contrast, psoriatic skin had significantly increased frequencies of TH1 and TH17 T cells compared with AD, whereas TH2 T cells were significantly elevated in AD. Distinct IL-22-producing CD4+ and CD8+ T-cell populations were significantly increased in AD skin compared with psoriasis. IL-22+CD8+ T-cell frequency correlated with AD disease severity.Conclusion Our data established that T cells could independently express IL-22 even with low expression levels of IL-17. This argues for a functional specialization of T cells such that "T17" and "T22" T-cells may drive different features of epidermal pathology in inflammatory skin diseases, including induction of antimicrobial peptides for "T17" T cells and epidermal hyperplasia for "T22" T-cells. Given the clinical correlation with disease severity, further characterization of "T22" T cells is warranted, and may have future therapeutic implications.
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“Circulating IL-22 correlates with the severity of AD and appears as a key driver in the inflammatory reaction116,119.”
From Atopic dermatitis: an expanding therapeutic pipeline for a complex disease (2022) · cites this paper as [116]
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“IL-22 is an important part of the transcriptomic signature in AD116,117.”
From Atopic dermatitis: an expanding therapeutic pipeline for a complex disease (2022) · cites this paper as [116]
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Atopic dermatitis: a review of evolving targeted therapies
Kalamaha, K., Reis, E., Newton, S. L., Roche, C., Julson, J. R., Fernandes, H., & Rodrigues, J. (2018) · Expert Review of Clinical Immunology · doi:10.1080/1744666x.2019.1560267 · Cited by 20
“Research over the next few years will likely focus on modulation or inhibition of certain cytokines, particularly IL-4, IL-13, IL-17, IL-31, and JAK-STAT inhibition.”
BackgroundInfluentialCurrent and emerging biologic and small molecule therapies for atopic dermatitis
Li, R., Hadi, S. M., & Guttman‐Yassky, E. (2019) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2019.1573422 · Cited by 20
“IL-22 CD8 + T-cells have been found to correlate with AD disease severity and analysis of AD lesions revealed significantly elevated levels of genes (P 0.005) associated with the Th22 pathway, including IL-22, IL-32, S100A7, S100A8, and S100A9 [1,108].”
InfluentialSelf-citationTh22 Cells Contribution in Immunopathogenesis of Rheumatic Diseases.
Azizi, G., Simhag, A., Rouby, N. M. E., & Mirshafiey, A. (2015) · PubMed · Cited by 20
Barnes, J. L., Plank, M. W., Asquith, K. L., Maltby, S., Sabino, L. R., Kaiko, G. E., Lochrin, A. J., Horvat, J. C., Mayall, J., Kim, R., et al. (2021) · Mucosal Immunology · doi:10.1038/s41385-021-00414-6 · Cited by 22
Expression of Helper and Regulatory T Cells in Atopic Dermatitis: A Meta-Analysis
Zhang, D.-J., Hao, F., Qian, T., & Cheng, H.-X. (2022) · Frontiers in Pediatrics · doi:10.3389/fped.2022.777992 · Cited by 21
“In our current study, the results were consistent with the previous studies, which demonstrated the percentage of IL-17-producing CD4 T cells in both skin specimens (26, 28) and peripheral blood (17) of patients with AD was increased.”
BackgroundResultPrebiotics in atopic dermatitis prevention and management
Lee, Y. H., Verma, N. K., & Thanabalu, T. (2021) · Journal of Functional Foods · doi:10.1016/j.jff.2021.104352 · Cited by 19
Chen, B.-R., Hsu, K.-T., Li, T., Chan, Y.-L., & Wu, C. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2021.108362 · Cited by 20
Gershater, M., Romero, R. J., Arenas‐Hernandez, M., Galaz, J., Motomura, K., Li, T., Xu, Y., Miller, D., Piqué-Regi, R., Martinez, G., et al. (2022) · The Journal of Immunology · doi:10.4049/jimmunol.2100439 · Cited by 19
Sabat, R., Witte, E., Witte, K., & Wolk, K. (2012) · Springer eBooks · doi:10.1007/978-3-0348-0522-3_2 · Cited by 22
“types include activated CD4 T cells [26–28], CD8 T cells [26, 29, 30], and gd T cells [31] as well as various innate lymphoid cells such as NK cells [26, 32–34], NKT cells [35, 36], lymphoid tissue inducer (LTi) [37, 38], and LTi-like cells [39, 40].”
BackgroundPonvilawan, B., Charoenngam, N., Wongtrakul, W., & Ungprasert, P. (2021) · Journal of Postgraduate Medicine · doi:10.4103/jpgm.jpgm_1270_20 · Cited by 18
“On the other hand, they had a downregulation of IL-2, one of the major cytokines of Th1 cells.[31-38] Moreover, recent studies have demonstrated an increased level of IgE among patients with SLE, particularly among those with active disease, similar to patients with AD.”
ResultCytokine and Chemokines Alterations in the Endemic Form of Pemphigus Foliaceus (Fogo Selvagem)
Timóteo, R. P., da Silva, M. V., da Silva, D. A. A., Catarino, J. D. S., Alves, F. H. C., Rodrigues, V., Roselino, A. M. F., Sales‐Campos, H., & Oliveira, C. J. F. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00978 · Cited by 18
“For this reason, it has been implicated in the pathogenesis of different inflammatory skin disorders including atopic dermatitis (28), psoriasis (29) and systemic lupus erythematosus with skin manifestations (30).”
BackgroundKabashima, K. (2012) · Dermatologica Sinica · doi:10.1016/j.dsi.2012.07.003 · Cited by 18
Altered plasma cytokines in dogs with atopic dermatitis
Mazrier, H., Vogelnest, L. J., Taylor, R. M., & Williamson, P. (2021) · Veterinary Dermatology · doi:10.1111/vde.13044 · Cited by 17
Yao, T., Wang, I., Sun, H., Ou, L.-S., Yu, H., Wang, L., & Hung, C. (2022) · Journal of Microbiology Immunology and Infection · doi:10.1016/j.jmii.2022.03.004 · Cited by 17
Czarnowicki, T., Kim, H. J., Villani, A. P., Glickman, J. W., DUCA, E. D., Han, J. K., Pavel, A. B., Lee, B. H., Rahman, A. H., Mérad, M., et al. (2021) · Allergy · doi:10.1111/all.14845 · Cited by 17
Self-citationKim, W., Koo, J., Cho, H., Lee, J.-U., Kim, J. Y., Lee, H., Lee, S., Kim, J. H., Oh, M. S., Suh, M., et al. (2017) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2017.04.007 · Cited by 19
“Recently, TH17 and TH22 lymphocyte subtypes were suggested to be involved in both AD and psoriasis.(16,17) Because the pathology of AD and psoriasis is mainly propagated by various inflammatory cytokine responses, modulation of cytokine signaling, effector T-cell function, or both is believed to be the most promising…”
BackgroundI don’t know about you, but I’m feeling IL-22
Dean, L., Threatt, A. N., Jones, K., Oyewole, E. O., Pauly, M., Wahl, M., Barahona, M., Reiter, R. W., & Nordgren, T. (2024) · Cytokine & growth factor reviews · doi:10.1016/j.cytogfr.2024.11.001 · Cited by 12
Advancing Therapeutic Strategies in Atopic Dermatitis: Emerging Targets and Personalized Approaches
Lo, Y., Cheng, T.-T., Huang, C., Cheng, Y., & Chyuan, I. (2025) · Biomolecules · doi:10.3390/biom15060838 · Cited by 16
“Elevated levels of IL-22 have been detected in both the serum and skin biopsies of patients with chronic AD [59,60].”
The Potential Role of T Helper Cell 22 and IL-22 in Immunopathogenesis of Multiple Sclerosis.
Fard, N. A., Azizi, G., & Mirshafiey, A. (2016) · PubMed Central · Cited by 16
Cui, D., Zhong, F., Lin, J., Wu, Y., Long, Q., Yang, X., Zhu, Q., Huang, L., Mao, Q., Huo, Z., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.14083 · Cited by 16
“Moreover, the sources of intracellular IL-22 were affected by other immune cells (such as CD8+T, NKT, γδT and macrophages) in EV71-associated HFMD patients, which will be further explored in a future studyinvolving IL-22 is an important cytokine in the regulation of tissue and cell responses during inflammation, and i…”
BackgroundInfluentialRook, A. H., Rook, K. A., & Lewis, D. J. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-55617-4_8 · Cited by 17
IL-23 and Th17 cells in infections and psoriasis
Kagami, S. (2011) · Japanese Journal of Clinical Immunology · doi:10.2177/jsci.34.13 · Cited by 15
Role of mesenchymal stem cells in the pathogenesis of psoriasis: current perspectives
Campanati, A., Consales, V., Orciani, M., Giuliodori, K., Ganzetti, G., Bobyr, I., Sorgentoni, G., Primio, R. D., & Offidani, A. (2017) · Psoriasis Targets and Therapy · doi:10.2147/ptt.s108311 · Cited by 16
“43 The activation of KCs and the formation of epidermal acanthosis – typical of psoriasis – are connected to IL-22.”
Autoreactive CD4+ T cells in patients with atopic dermatitis
James, E. A., & Kwok, W. W. (2011) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2011.05.005 · Cited by 16
Revisiting Therapies for Atopic Dermatitis that Failed Clinical Trials
Agnihotri, G., & Lio, P. A. (2020) · Clinical Drug Investigation · doi:10.1007/s40261-020-00905-7 · Cited by 15
Heeringa, J. J., Fieten, K. B., Bruins, F. M., van Hoffen, E., Knol, E. F., Pasmans, S. G. M. A., & van Zelm, M. C. (2018) · Clinical & Experimental Allergy · doi:10.1111/cea.13136 · Cited by 15
“The production of IL-22 induces epidermal hyperplasia through their effect on keratinocytes, whereas Th2 cytokines induce barrier disruption.(17,25) Furthermore, regulatory T cells (Tregs) are consistently found to be increased in blood of patients with AD.”
BackgroundPinget, G. V., Tan, J., Niewold, P., Mazur, E., Angelatos, A. S., King, N. J. C., & Macia, L. (2020) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2020.03.973 · Cited by 14
Eminel, S., Jin, N., Rostami, M., Dibbert, S., Mrowietz, U., & Suhrkamp, I. (2016) · Experimental Dermatology · doi:10.1111/exd.13138 · Cited by 18
Dupilumab para el tratamiento de la dermatitis atópica
Ferreira, S., & Torres, T. R. (2018) · Actas Dermo-Sifiliográficas · doi:10.1016/j.ad.2017.10.012 · Cited by 15
Monoclonal antibodies for the treatment of atopic dermatitis
Renert‐Yuval, Y., & Guttman‐Yassky, E. (2018) · Current Opinion in Allergy and Clinical Immunology · doi:10.1097/aci.0000000000000455 · Cited by 15
Self-citationA comparison of inflammatory mediator expression between palmoplantar pustulosis and pompholyx
Kim, D. Y., Kim, J. Y., Kim, T., Kwon, J. E., Sohn, H., Park, J. H., Lim, B. J., & Oh, S. H. (2013) · Journal of the European Academy of Dermatology and Venereology · doi:10.1111/jdv.12203 · Cited by 15
Metadata
- Authors
- Nograles, K. E., Zaba, L. C., Shemer, A., Fuentes-Duculan, J., Cardinale, I., Kikuchi, T., Ramon, M., Bergman, R., Krueger, J. G., & Guttman-Yassky, E.
- Affiliations
- Rockefeller University (US)
- Technion – Israel Institute of Technology (IL)
- Venue
- Journal of Allergy and Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2009-06
- Volume
- 123
- Issue
- 6
- Pages
- 1244-1252.e2
- ISSN
- 0091-6749 (ISSN-L)
- PMC
- PMC2874584
- OpenAlex
- W2164098277
- Cited by
- 627
- References
- 30
- Citations by year
- 2026: 13 · 2025: 17 · 2024: 21 · 2023: 23 · 2022: 28 · 2021: 39 · 2020: 39 · 2019: 28 · 2018: 25 · 2017: 49 · 2016: 49 · 2015: 51 · 2014: 52 · 2013: 34 · 2012: 47
- FWCI
- 65.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Allergy and Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (GM 07739, T32GM007739)
- National Center for Research Resources (UL1RR024143)
- Topics
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- atopic dermatitis, IL-22, IL-17, Th17 cells, Th2 cells, Th1 cells, IL-23, psoriasis, CD4+ T cells, CD8+ T cells, disease severity, epidermal hyperplasia, antimicrobial peptides, skin inflammation
- MeSH terms
- Interleukin-22, Adult, Chronic Disease, Dermatitis, Atopic, T-Lymphocytes, Helper-Inducer, Humans, Interleukins, Middle Aged, Psoriasis, T-Lymphocyte Subsets, Interleukin-17, Interleukin-23
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