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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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Liang, S. C., Tan, X.-Y., Luxenberg, D. P., Karim, R., Dunussi-Joannopoulos, K., Collins, M., & Fouser, L. A. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20061308 · Cited by 2,330
The skin: an indispensable barrier
Proksch, E., Brandner, J. M., & Jensen, J. (2008) · Experimental Dermatology · doi:10.1111/j.1600-0625.2008.00786.x · Cited by 2,054
Interleukin-22, a TH17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis
Zheng, Y., Danilenko, D. M., Valdez, P. A., Kasman, I. M., Eastham‐Anderson, J., Wu, J., & Ouyang, W. (2006) · Nature · doi:10.1038/nature05505 · Cited by 1,886
Psoriasis Vulgaris Lesions Contain Discrete Populations of Th1 and Th17 T Cells
Lowes, M. A., Kikuchi, T., Fuentes‐Duculan, J., Cardinale, I. R., Zaba, L. C., Haider, A. S., Bowman, E. P., & Krueger, J. G. (2008) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5701213 · Cited by 1,085
Self-citationCytokine modulation of atopic dermatitis filaggrin skin expression
Howell, M. D., Kim, B. E., Gao, P., Grant, A. V., Boguniewicz, M., DeBenedetto, A., Schneider, L., Beck, L. A., Barnes, K. C., & Leung, D. Y. M. (2007) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2007.04.031 · Cited by 1,084
Boniface, 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
Nograles, K. E., Zaba, L. C., Guttman‐Yassky, E., Fuentes‐Duculan, J., Suárez‐Fariñas, M., Cardinale, I. R., Khatcherian, A., Gonzalez, J., Pierson, K. C., White, T. R., et al. (2008) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2008.08769.x · Cited by 816
Self-citationPossible Pathogenic Role of Th17 Cells for Atopic Dermatitis
Koga, C., Kabashima, K., Shiraishi, N., Kobayashi, M., & TOKURA, Y. (2008) · Journal of Investigative Dermatology · doi:10.1038/jid.2008.111 · Cited by 680
Ma, H., Liang, S. C., Li, J., Napierata, L., Brown, T., Benoit, S., Senices, M., Gill, D. S., Dunussi‐Joannopoulos, K., Collins, M. A., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci33263 · Cited by 555
Loricrin and involucrin expression is down-regulated by Th2 cytokines through STAT-6
Kim, B. E., Leung, D. Y. M., Boguniewicz, M., & Howell, M. D. (2008) · Clinical Immunology · doi:10.1016/j.clim.2007.11.006 · Cited by 538
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Items 101–200 of 626
Skin Immune Landscape: Inside and Outside the Organism
Abdallah, F., Mijouin, L., & Pichon, C. (2017) · Mediators of Inflammation · doi:10.1155/2017/5095293 · Cited by 181
“disorders are caused by the deregulation of TH17 and TH22 immune responses leading to both psoriasis and atopic dermatitis [94, 98, 99].”
BackgroundThe Role and Diagnosis of Allergic Contact Dermatitis in Patients with Atopic Dermatitis
Owen, J. L., Vakharia, P. P., & Silverberg, J. I. (2018) · American Journal of Clinical Dermatology · doi:10.1007/s40257-017-0340-7 · Cited by 163
Mechanisms underlying helper T-cell plasticity: Implications for immune-mediated disease
Hirahara, K., Poholek, A. C., Vahedi, G., Laurence, A. D. J., Kanno, Y., Milner, J. D., & O’Shea, J. J. (2013) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2013.03.015 · Cited by 171
Petrolatum: Barrier repair and antimicrobial responses underlying this “inert” moisturizer
Czarnowicki, T., Malajian, D., Khattri, S., Correa da Rosa, J., Dutt, R., Finney, R., Dhingra, N., Xiangyu, P., Xu, H., Estrada, Y. D., et al. (2016) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2015.08.013 · Cited by 161
Self-citationSystemic Treatment of Adult Atopic Dermatitis: A Review
Megna, M., Napolitano, M., Patruno, C., Villani, A., Balato, A., Monfrecola, G., Ayala, F., & Balato, N. (2016) · Dermatology and Therapy · doi:10.1007/s13555-016-0170-1 · Cited by 161
“Therefore, ustekinumab may be useful in AD, which is increasingly recognized as a Th2- and Th22-centered disease with some contributions of the Th17 and Th1 axes [97].”
BackgroundCho, K., Suh, J. W., Lee, K. H., Kang, J. L., & Woo, S. (2011) · International Immunology · doi:10.1093/intimm/dxr110 · Cited by 155
Meyer, N., Zimmermann, M., Bürgler, S., Bassin, C., Woehrl, S., Moritz, K. B., Rhyner, C., Indermitte, P., Schmid‐Grendelmeier, P., Akdiş, M., et al. (2010) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2010.01.016 · Cited by 151
IL-17 and IL-22 in atopic allergic disease
Souwer, Y., Szegedi, K., Kapsenberg, M. L., & de Jong, E. C. (2010) · Current Opinion in Immunology · doi:10.1016/j.coi.2010.10.013 · Cited by 154
Biologics for Treatment of Atopic Dermatitis: Current Status and Future Prospect
Ratchataswan, T., Banzon, T. M., Thyssen, J. P., Weidinger, S., Guttman‐Yassky, E., & Phipatanakul, W. (2021) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2020.11.034 · Cited by 152
Self-citationFujita, H., Shemer, A., Suárez‐Fariñas, M., Johnson-Huang, L. M., Tintle, S. J., Cardinale, I. R., Fuentes‐Duculan, J., Novitskaya, I., Carucci, J. A., Krueger, J. G., et al. (2011) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2011.05.016 · Cited by 147
Self-citationMolecular Mechanisms of Cutaneous Inflammatory Disorder: Atopic Dermatitis
Kim, J. E., Kim, J., Cho, D., & Park, H. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17081234 · Cited by 153
“The relative absence of IL-17 in AD lesions may be related to reduced AMP levels and may explain the increased susceptibility to skin infection in patients with AD [129].”
BackgroundBiological and pathological activities of interleukin-22
Lanfranca, M. P., Lin, Y., Fang, J., Zou, W., & Frankel, T. L. (2016) · Journal of Molecular Medicine · doi:10.1007/s00109-016-1391-6 · Cited by 146
Lou, H., Lu, J., Choi, E. B., Oh, M. H., Jeong, M., Barmettler, S., Zhu, Z., & Zheng, T. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1600126 · Cited by 140
“, FLG and loricrin) (6, 53) and induces proinflammatory gene expression of the S100 family of calcium-binding proteins in human epidermal keratinocytes (53).”
BackgroundAn Update on the Pathophysiology of Atopic Dermatitis
Malik, K., Heitmiller, K., & Czarnowicki, T. (2017) · Dermatologic Clinics · doi:10.1016/j.det.2017.02.006 · Cited by 140
“IL-17 is a known inducer of AMPs in keratinocytes.(59) Relatively reduced”
BackgroundRole of Th22 Cells in the Pathogenesis of Autoimmune Diseases
Jiang, Q., Yang, G., Xiao, F., Xie, J., Wang, S., Lu, L., & Cui, D. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.688066 · Cited by 145
Fonacier, L. S., Dreskin, S. C., & Leung, D. Y. M. (2010) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2009.05.039 · Cited by 139
“However, their expression is significantly less than that seen in patients with psoriasis.(89) Furthermore, TH2 cytokines, such as IL-4 and IL-13, inhibit IL-17–induced effects on generation of AMPs by keratinocytes.”
Eyerich, S., Wagener, J., Wenzel, V., Scarponi, C., Pennino, D., Albanesi, C., Schaller, M., Behrendt, H., Ring, J., Schmidt‐Weber, C. B., et al. (2011) · European Journal of Immunology · doi:10.1002/eji.201041197 · Cited by 139
A Double Edged Sword Role of Interleukin-22 in Wound Healing and Tissue Regeneration
Arshad, T., Mansur, F., Pálek, R., Manzoor, S., & Liška, V. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.02148 · Cited by 138
“Pro-inflammatory activity performed by IL-22 has also been associated with several inflammatory diseases such as psoriasis and atopic dermatitis (61, 62).”
BackgroundMusolino, C., Allegra, A., Innao, V., Allegra, A. G., Pioggia, G., & Gangemi, S. (2017) · Mediators of Inflammation · doi:10.1155/2017/1852517 · Cited by 168
“Di Lullo et al. discovered that the incidence of IL-22 T cells was significantly augmented in PB and BM of stage III and relapsedMM subjects, compared with donors or subjects with asymptomatic or stage I/II MM. Th22 cells derived from the BM ofMM subjects produced IL-22 and IL-13 but not IL17.”
BackgroundPfaff, C. M., Marquardt, Y., Fietkau, K., Baron, J. M., & Lüscher, B. (2017) · Scientific Reports · doi:10.1038/s41598-017-15892-7 · Cited by 135
Organization of the skin immune system and compartmentalized immune responses in infectious diseases
Quaresma, J. A. S. (2019) · Clinical Microbiology Reviews · doi:10.1128/cmr.00034-18 · Cited by 149
Immunology of IL-12: An update on functional activities and implications for disease
Ullrich, K. A.-M., Schulze, L. L., Paap, E.-M., Müller, T. M., Neurath, M. F., & Zundler, S. (2020) · EXCLI journal · doi:10.17179/excli2020-3104 · Cited by 148
“…since TH17 cells were predominantly found in the dermis of psoriatic skin lesions (Yawalkar et al., 2009; Lowes et al., 2008), and IL-22 expression was also increased (Nograles et al., 2009), suggesting that besides TH1 cells, TH17 and TH22 cells have a major influence on disease development.”
BackgroundPutting together the psoriasis puzzle: an update on developing targeted therapies
Johnson-Huang, L. M., Lowes, M. A., & Krueger, J. G. (2012) · Disease Models & Mechanisms · doi:10.1242/dmm.009092 · Cited by 134
“Th17 cells have also been shown to be the main producers of IL-22, although recently, cells that exclusively produce IL-22 (termed Th22 cells) have been identified as a distinct Th cell subset that is present in lesional psoriatic skin (Eyerich et al., 2009; Nograles et al., 2009; Trifari et al., 2009).”
BackgroundSelf-citationBernard, F., Morel, F., Camus, M., Pedretti, N., Barrault, C., Garnier, J., & Lecron, J. (2012) · Journal of Allergy · doi:10.1155/2012/718725 · Cited by 140
Endophenotypic Variations of Atopic Dermatitis by Age, Race, and Ethnicity
Nomura, T., Wu, J., Kabashima, K., & Guttman‐Yassky, E. (2020) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2020.02.022 · Cited by 130
Self-citationZhuang, Y., Peng, L., Zhao, Y., Shi, Y., Mao, X., Guo, G., Chen, W., Liu, X., Zhang, J., Liu, T., et al. (2012) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-012-1241-5 · Cited by 136
“Although some IL-22CD4 T cells also produce other cytokines such as IL-17 [5], some IL-22CD4 T cells”
BackgroundMild atopic dermatitis lacks systemic inflammation and shows reduced nonlesional skin abnormalities
He, H., DUCA, E. D., Diaz, A., Kim, H. J., Gay-Mimbrera, J., Zhang, N., Wu, J., Beaziz, J., Estrada, Y. D., Krueger, J. G., et al. (2020) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2020.08.041 · Cited by 127
Self-citationBrüggen, M., Klein, I., Greinix, H., Bauer, W. M., Kuzmina, Z. J., Rabitsch, W., Kalhs, P., Petzelbauer, P., Knobler, R., Stingl, G., et al. (2013) · Blood · doi:10.1182/blood-2013-07-514372 · Cited by 126
Interleukin-17A Promotes IgE Production in Human B Cells
Milovanović, M., Drozdenko, G., Weise, C., Babina, M., & Worm, M. (2010) · Journal of Investigative Dermatology · doi:10.1038/jid.2010.175 · Cited by 126
“It was recently established that T cells can independently express IL-22 (a Th17-related cytokine), and that these ‘‘T22’’ cells may be important for AD severity (Nograles et al., 2009).”
BackgroundNew treatments for atopic dermatitis targeting beyond IL-4/IL-13 cytokines
Renert‐Yuval, Y., & Guttman‐Yassky, E. (2019) · Annals of Allergy Asthma & Immunology · doi:10.1016/j.anai.2019.10.005 · Cited by 126
Self-citationMansouri, Y., & Guttman‐Yassky, E. (2015) · Journal of Clinical Medicine · doi:10.3390/jcm4050858 · Cited by 129
“This may be explained by the effects of the IL-22 cytokine [65].”
BackgroundSelf-citationNew Insights on CD8+ T Cells in Inflammatory Bowel Disease and Therapeutic Approaches
Casalegno‐Garduño, R., & Däbritz, J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.738762 · Cited by 124
T-cell Subset Regulation in Atopy
Jutel, M., & Akdiş, C. A. (2011) · Current Allergy and Asthma Reports · doi:10.1007/s11882-011-0178-7 · Cited by 125
“influencing the course of inflammatory epithelial diseases [82].”
Moy, A. P., Murali, M. R., Kroshinsky, D., Duncan, L. M., & Nazarian, R. M. (2015) · JAMA Dermatology · doi:10.1001/jamadermatol.2015.2 · Cited by 123
Increased frequencies of IL‐31‐producing T cells are found in chronic atopic dermatitis skin
Szegedi, K., Kremer, A. E., Kežić, S., Teunissen, M. B. M., Bos, J. D., Luiten, R. M., Res, P. C., & Middelkamp-Hup, M. A. (2012) · Experimental Dermatology · doi:10.1111/j.1600-0625.2012.01487.x · Cited by 121
The Role of Cytokines/Chemokines in the Pathogenesis of Atopic Dermatitis
Yamanaka, K., & Mizutani, H. (2011) · Current problems in dermatology · doi:10.1159/000323299 · Cited by 120
Evolution of pathologic T-cell subsets in patients with atopic dermatitis from infancy to adulthood
Czarnowicki, T., He, H., Canter, T., Han, J., Lefferdink, R., Erickson, T., Rangel, S., Kameyama, N., Kim, H. J., Pavel, A. B., et al. (2020) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2019.09.031 · Cited by 118
“CD8(1) T cells are major producers of IL-22 in the skin of adults with AD.(69) Lower proportions of CD8(1) versus CD4(1) cells in early childhood(46,70) and the fact that IL-22 marks AD chronicity(42) might explain why skin-homing TH22/TC22 cell frequencies are highest in adolescents and adults.”
BackgroundSelf-citationNuclear localization of activated STAT6 and STAT3 in epidermis of prurigo nodularis
Fukushi, S., Yamasaki, K., & Aiba, S. (2011) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2011.10498.x · Cited by 117
Single-cell analysis reveals innate lymphoid cell lineage infidelity in atopic dermatitis
Alkon, N., Bauer, W. M., Krausgruber, T., Goh, I., Griss, J., Nguyen, V., Reininger, B., Bangert, C., Staud, C. J., Brunner, P. M., et al. (2021) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2021.07.025 · Cited by 125
“In this context, it should be remembered that the bulk analysis of AD skin biopsies at the mRNA and protein levels, although regularly showing the signs of type 2 inflammation, also revealed the presence of other cytokine gene signatures under certain conditions.(61) IL-17A, for example, was detected in skin biopsies…”
BackgroundThe Biology and Functions of Th22 Cells
Jia, L., & Wu, C. Y. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-94-017-9487-9_8 · Cited by 125
Olivry, T., Mayhew, D. N., Paps, J. S., Linder, K. E., Peredo, C. E., Rajpal, D. K., Hofland, H. E. J., & Cote-Sierra, J. (2016) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2016.05.117 · Cited by 115
Synergy of Interleukin (IL)-5 and IL-18 in eosinophil mediated pathogenesis of allergic diseases
Kandikattu, H. K., Venkateshaiah, S. U., & Mishra, A. (2019) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2019.05.003 · Cited by 121
“IL-22 in lesioned skin of chronic AD is higher than in psoriatic lesions [149], IL-22 elevated in asthma patients and the mouse model of asthma [150, 151].”
BackgroundTh22 in inflammatory and autoimmune disease: prospects for therapeutic intervention
Zhang, N., Pan, H., & Ye, D. (2011) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-011-0772-y · Cited by 119
“Actually, the expression of IL-22 in atopic skin was even slightly higher when compared to lesional psoriatic skin, which may rely on the observation that the majority of IL-22-producing cells in atopic skin are Th22 cells, whereas in psoriatic skin there is a shift to a rather equal presence of IL-22-producing Th22,…”
BackgroundResultNew pathogenic and therapeutic paradigms in atopic dermatitis
Malajian, D., & Guttman‐Yassky, E. (2014) · Cytokine · doi:10.1016/j.cyto.2014.11.023 · Cited by 115
“with disease severity, especially among Tc22 cells [75].”
BackgroundInfluentialSelf-citationStaphylococcal exotoxins are strong inducers of IL-22: A potential role in atopic dermatitis
Niebuhr, M., Scharonow, H., Gathmann, M., Mamerow, D., & Werfel, T. (2010) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2010.07.041 · Cited by 110
Mashiko, S., Mehta, H., Bissonnette, R., & Sarfati, M. (2017) · Journal of Dermatological Science · doi:10.1016/j.jdermsci.2017.07.003 · Cited by 114
Interleukin-22: A likely target for treatment of autoimmune diseases
Yang, X., & Zheng, S. G. (2014) · Autoimmunity Reviews · doi:10.1016/j.autrev.2013.11.008 · Cited by 116
“Upregulated expression of IL-22 was present in the skin from AD patients [48].”
BackgroundAtopic dermatitis: pathogenesis
Guttman‐Yassky, E., Waldman, A. R., Ahluwalia, J., Ong, P. Y., & Eichenfield, L. F. (2017) · Seminars in Cutaneous Medicine and Surgery · doi:10.12788/j.sder.2017.036 · Cited by 113
Self-citationTakahashi, K., Hirose, K., Kawashima, S., Niwa, Y., Wakashin, H., Iwata, A., Tokoyoda, K., Renauld, J., Iwamoto, I., Nakayama, T., et al. (2011) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2011.06.018 · Cited by 113
IL-22, but Not IL-17, Dominant Environment in Cutaneous T-cell Lymphoma
Miyagaki, T., Sugaya, M., Suga, H., Kamata, M., Ohmatsu, H., Fujita, H., Asano, Y., Tada, Y., Kadono, T., & Sato, S. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-1192 · Cited by 110
“It was recently demonstrated that IL-22-expressing T cells are increased in the lesional skin of AD patients (26).”
BackgroundNew era of biologic therapeutics in atopic dermatitis
Guttman‐Yassky, E., Dhingra, N., & Leung, D. Y. M. (2013) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2013.758708 · Cited by 103
“The immune infiltrates in chronic AD skin lesions have been shown to be primarily composed of Th2 and Th22 T cells, although Th1 and Th17 T cells are also present [10].”
BackgroundInfluentialSelf-citationThe Many Faces of CD4+ T Cells: Immunological and Structural Characteristics
Chatzileontiadou, D. S. M., Sloane, H., Nguyen, A., Gras, S., & Grant, E. J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms22010073 · Cited by 109
Yoon, J., Leyva-Castillo, J. M., Wang, G., Galand, C., Oyoshi, M. K., Kumar, L., Hoff, S., He, R., Chervonsky, A. V., Oppenheim, J. J., et al. (2016) · The Journal of Experimental Medicine · doi:10.1084/jem.20150376 · Cited by 101
“Moreover, AD skin lesions demonstrate elevated levels of the endogenous TLR4 ligands IL-23 and IL-22 (Guttman-Yassky et al., 2008; Nograles et al., 2009; Gittler et al., 2012), and serum IL-22 levels are elevated in AD (Hayashida et al.”
BackgroundInfluentialLiu, T., Peng, L., Yu, P.-W., Zhao, Y., Shi, Y., Mao, X., Chen, W., Cheng, P., Wang, T., Chen, N., et al. (2012) · Journal of Clinical Immunology · doi:10.1007/s10875-012-9718-8 · Cited by 103
“In these studies, Th22 cells were shown to increase in both the inflamed skin lesions and the peripheral blood of the patients with a positive correlation with disease severity [14, 15, 17].”
Dendritic cells: Bridging innate and adaptive immunity in atopic dermatitis
Novak, N., Koch, S., Allam, J., & Bieber, T. R. M. (2010) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2009.11.019 · Cited by 101
Natural killer cells in atopic and autoimmune diseases of the skin
von Bubnoff, D., Andrès, E., Hentges, F., Bieber, T. R. M., Michel, T., & Zimmer, J. (2010) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2009.11.020 · Cited by 101
Molecular Biology of Atopic Dermatitis
Mu, Z., Zhao, Y. P., Liu, X., Chang, C. C.-C., & Zhang, J. (2014) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-014-8415-1 · Cited by 101
“In chronic AD, IL-17 expression is reduced, or even undetectable [227].”
BackgroundDrug Evaluation Review: Dupilumab in Atopic Dermatitis
Hamilton, J. D., Ungar, B., & Guttman‐Yassky, E. (2015) · Immunotherapy · doi:10.2217/imt.15.69 · Cited by 94
Self-citationBrüggen, M., Bauer, W. M., Reininger, B., Clim, E., Captarencu, C., Steiner, G., Brunner, P. M., Meier-Schiesser, B., French, L. E., & Stingl, G. (2016) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2016.07.017 · Cited by 93
“In analogy to the role of Th22 cells in AD (Czarnowicki et al., 2015; Nograles et al., 2009), IL-22 producing ILC3 could be coresponsible not only for inflammation but also for lichenification of the skin, a hallmark of AD (Zheng et al.”
BackgroundInfluentialDer p 1‐specific regulatory T‐cell response during house dust mite allergen immunotherapy
Boonpiyathad, T., Sokołowska, M., Morita, H., Rückert, B., Kast, J. I., Wawrzyniak, M., Sangasapaviliya, A., Pradubpongsa, P., Fuengthong, R., Thantiworasit, P., et al. (2018) · Allergy · doi:10.1111/all.13684 · Cited by 92
“However, an uncontrolled output of IL‐22 may lead to inflammation that has been observed in several diseases including atopic dermatitis, psoriasis, or rheumatoid arthritis.(54) IL‐22 is a member of the IL‐10 cytokine family but is usually detected in Th17 cells together with the production of IL‐ 17 and type 3 innate…”
BackgroundZhang, S., Fujita, H., Mitsui, H., Yanofsky, V. R., Fuentes‐Duculan, J., Pettersen, J. S., Suárez‐Fariñas, M., Gonzalez, J., Wang, C. Q. F., Krueger, J. G., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0062154 · Cited by 93
“IL-22 is traditionally thought to be produced by CD4+ helper T lymphocytes (Th) including Th1, Th17, and Th22, however a subset of CD8+ cytotoxic T cells (Tc22) have also been shown to produce this cytokine [10,11,12,13].”
BackgroundSelf-citationAerts, N. E., Knop, K. J. D., Leysen, J., Ebo, D. G., Bridts, C. H., Weyler, J., Stevens, W. J., & Clerck, L. S. D. (2010) · Lara D. Veeken · doi:10.1093/rheumatology/keq224 · Cited by 91
Dong, C., Virtucio, C., Zemska, O., Baltazar, G., Zhou, Y., Baía, D., Jones-Iatauro, S., Sexton, H., Martin, S., Dee, J., et al. (2016) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.116.232819 · Cited by 90
“Overproduction of IL-22 stimulates the proliferation of keratinocytes and prevents their terminal differentiation, thus contributing to epidermal hyperplasia (Boniface et al., 2005; Sa et al., 2007;Nograles et al., 2009;Guttman-Yassky et al., 2011b; Lowes, et al., 2013; Martin et al., 2013).”
BackgroundThe critical role of macrophages in the pathogenesis of hidradenitis suppurativa
Shah, A., Alhusayen, R. O., & Amini‐Nik, S. (2017) · Inflammation Research · doi:10.1007/s00011-017-1074-y · Cited by 92
“Overexpression of IL-22-producing CD8-positive T cells has been associated with inflammatory skin conditions such as psoriasis [67] and atopic dermatitis [68].”
BackgroundThe mesenchymal stem cell profile in psoriasis
Orciani, M., Campanati, A., Salvolini, E., Lucarini, G., Benedetto, G. D., Offidani, A., & Primio, R. D. (2011) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2011.10438.x · Cited by 85
Staphylococcal Alpha-Toxin Is a Strong Inducer of Interleukin-17 in Humans
Niebuhr, M., Gathmann, M., Scharonow, H., Mamerow, D., Mommert, S., Balaji, H., & Werfel, T. (2011) · Infection and Immunity · doi:10.1128/iai.00958-10 · Cited by 84
“They could show no differences in IL-17A, IL-22, IL-4, and IFN- secretion in CD4 and CD8 T cells obtained from the peripheral blood of PS patients and AD patients (35).”
BackgroundTSLP is a direct trigger for T cell migration in filaggrin-deficient skin equivalents
Wallmeyer, L., Dietert, K., Sochorová, M., Gruber, A. D., Kleuser, B., Vávrová, K., & Hedtrich, S. (2017) · Scientific Reports · doi:10.1038/s41598-017-00670-2 · Cited by 82
Alkon, N., Assen, F. P., Arnoldner, T., Bauer, W. M., Medjimorec, M. A., Shaw, L. E., Rindler, K., Holzer, G., Weber, P. B., Weninger, W. J., et al. (2023) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2023.04.019 · Cited by 83
An update on the role of human dendritic cells in patients with atopic dermatitis
Novak, N. (2012) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2012.01.062 · Cited by 82
Sertorio, M. G., Hou, X., do Carmo, R. F., Dessein, H., Cabantous, S., Abdelwahed, M., Romano, A., de Albuquerque, F. M., Vasconcelos, L. R. S., Carmo, T. M. A., et al. (2014) · Hepatology · doi:10.1002/hep.27629 · Cited by 82
“This suggests that IL-22 is probably produced by Th22 cells (23, 24) and NK-like innate”
Atopic Dermatitis Studies through In Vitro Models
Vuyst, É. D., Salmon, M., Evrard, C., de Rouvroit, C. L., & Poumay, Y. (2017) · Frontiers in Medicine · doi:10.3389/fmed.2017.00119 · Cited by 80
“Regarding Th22 cells, these are also reported as increased in AD skin and correlated with disease severity (126).”
BackgroundYang, Z., Kim, H. J., Villasboas, J. C., Price-Troska, T. L., Jalali, S., Wu, H., Luchtel, R. A., Polley, M. C., Novak, A. J., & Ansell, S. M. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.01.085 · Cited by 77
Schwartz, C., Moran, T., Saunders, S. P., Kaszlikowska, A., Floudas, A., Bom, J., Núñez, G., Iwakura, Y., O'Neill, L. A. J., Irvine, A. D., et al. (2019) · Allergy · doi:10.1111/all.13801 · Cited by 76
da Rosa, J. C., Malajian, D., Shemer, A., Rozenblit, M., Dhingra, N., Czarnowicki, T., Khattri, S., Ungar, B., Finney, R., Xu, H., et al. (2015) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2014.11.017 · Cited by 74
Self-citationAtopic dermatitis: the role of Langerhans cells in disease pathogenesis
Dubrac, S., Schmuth, M., & Ebner, S. (2010) · Immunology and Cell Biology · doi:10.1038/icb.2010.33 · Cited by 76
Psoriasis and other Th17-mediated skin diseases
TOKURA, Y., MORI, T., & HINO, R. (2010) · Journal of UOEH · doi:10.7888/juoeh.32.317 · Cited by 73
Nakagome, K., Imamura, M., Kawahata, K., Harada, H., Okunishi, K., Matsumoto, T., Sasaki, O., Tanaka, R., Kano, M. R., Chang, H., et al. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1001560 · Cited by 76
The Central Roles of Keratinocytes in Coordinating Skin Immunity
Simmons, J., & Gallo, R. L. (2024) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2024.06.1280 · Cited by 79
Treatment of Eczema: Corticosteroids and Beyond
Chong, M., & Fonacier, L. S. (2015) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-015-8486-7 · Cited by 73
Xue, L., Fergusson, J. R., Salimi, M., Panse, I., Ussher, J. E., Hegazy, A. N., Vinall, S. L., Jackson, D. G., Hunter, M., Pettipher, R., et al. (2014) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2014.09.006 · Cited by 75
“IL22–producing cells and plasma concentrations of IL-22 are increased with the severity of atopic dermatitis and asthma.(32,33) GM-CSF is critical for granulocyte survival and enhances their activities.”
BackgroundOleanolic acid acetate inhibits atopic dermatitis and allergic contact dermatitis in a murine model
Choi, J. K., Oh, H., Lee, S., Park, J., Khang, D., Lee, S. W., Lee, W. S., Rho, M., & Kim, S. (2013) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2013.03.001 · Cited by 71
Pathophysiology of Atopic Dermatitis and Psoriasis: Implications for Management in Children
Chovatiya, R., & Silverberg, J. I. (2019) · Children · doi:10.3390/children6100108 · Cited by 74
“Th22 cells, a more recently described subset of T-cells that show an increased number and activity in AD lesions, produce high levels of IL-22 that may induce epidermal hyperplasia and terminal keratinocyte differentiation [89].”
BackgroundYamamura, Y., Nakashima, C., & Otsuka, A. (2024) · Frontiers in Medicine · doi:10.3389/fmed.2024.1342176 · Cited by 74
Human β-defensin-2 enhances IFN-γ and IL-10 production and suppresses IL-17 production in T cells
Kanda, N., Kamata, M., Tada, Y., Ishikawa, T., Sato, S., & Watanabe, S. (2011) · Journal of Leukocyte Biology · doi:10.1189/jlb.0111004 · Cited by 71
“IL-22 is produced not only by Th17 cells but also by Th1 [44] or CD8 T cells [45] and by Th22 cells [12].”
BackgroundTh17 Differentiation and Their Pro-inflammation Function
Song, X., Gao, H., & Qian, Y. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-94-017-9487-9_5 · Cited by 70
“Increased IL-22 expression was found in both atopic dermatitis (AD) patients and asthmatic patients [201, 217].”
BackgroundAkdis, M. (2009) · Current Opinion in Immunology · doi:10.1016/j.coi.2009.07.012 · Cited by 68
Mastelic, B., do Rosário, A. P. F., Veldhoen, M., Renauld, J., Jarra, W., Sponaas, A., Roetynck, S., Stockinger, B., & Langhorne, J. (2012) · Frontiers in Immunology · doi:10.3389/fimmu.2012.00085 · Cited by 68
Regulation of Dendritic Cell Function in Inflammation
Said, A., & Weindl, G. (2015) · Journal of Immunology Research · doi:10.1155/2015/743169 · Cited by 71
“In addition to Th2/Th1 activity, Th22 cells appear in high numbers in lesional AD skin, where a correlation between disease severity and increase of Th22 cells is described [170, 171].”
BackgroundTh17 cells and tissue remodeling in atopic and contact dermatitis
Simon, D., Aeberhard, C., Erdemoglu, Y., & Simon, H. (2013) · Allergy · doi:10.1111/all.12351 · Cited by 70
“In AD, the expression of IL-22 in the skin is higher than in psoriasis that predominantly exhibits IL-17 expression (19).”
BackgroundReed, J. L., Scott, D. E., & Bray, M. (2012) · Clinical Infectious Diseases · doi:10.1093/cid/cir952 · Cited by 69
Role of IL-22 in homeostasis and diseases of the skin
Lopez, D. V., & Kongsbak‐Wismann, M. (2022) · Apmis · doi:10.1111/apm.13221 · Cited by 66
“ing from severe AD than in patients suffering from psoriasis [49,51].”
BackgroundInducible NO synthase and antibacterial host defence in times of Th17/Th22/T22 immunity
Mühl, H., Bachmann, M., & Pfeilschifter, J. M. (2010) · Cellular Microbiology · doi:10.1111/j.1462-5822.2010.01559.x · Cited by 66
“Accordingly, cytokine responses characterized by lack of IL-17 along with CD4+/ CD8+ T cell-derived IL-22 production were introduced as T22-like cytokine responses (Nograles et al., 2009; Bachmann et al., 2010).”
BackgroundBiological Treatments in Atopic Dermatitis
Montes‐Torres, A., Llamas‐Velasco, M., Pérez-Plaza, A., Solano-López, G., & Sánchez-Pérez, J. (2015) · Journal of Clinical Medicine · doi:10.3390/jcm4040593 · Cited by 66
“demonstrated an elevation of IL-22 expression in AD lesional skin compared to normal and psoriatic skin biopsies [69].”
BackgroundKanda, N., & Watanabe, S. (2011) · Immunobiology · doi:10.1016/j.imbio.2011.10.010 · Cited by 65
Kanda, N., Hau, C. S., Tada, Y., Sato, S., & Watanabe, S. (2012) · Allergy · doi:10.1111/j.1398-9995.2012.02824.x · Cited by 66
“IL-22, produced by T-cell subpopulation in AD lesions (15), induces the proliferation of keratinocytes (1, 15).”
BackgroundT cell immunity in the teleost digestive tract
Tafalla, C., Leal, E., Yamaguchi, T., & Fischer, U. (2016) · Developmental & Comparative Immunology · doi:10.1016/j.dci.2016.02.019 · Cited by 69
Fang, Z., Pan, T., Wang, H., Zhu, J., Zhang, H., Zhao, J., Chen, W., & Lu, W. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23147735 · Cited by 65
“However, increased IL-22 is positively related to the development of AD via modulating the gene expression of the skin barrier-related molecules including filaggrin, loricrin, and involucrin [32], and its main producers are Th22 cells that do not produce IL-17A [33].”
BackgroundThe role of IL-23 in the immunopathogenesis of psoriasis
Meglio, P. D., & Nestle, F. O. (2010) · F1000 Biology Reports · doi:10.3410/b2-40 · Cited by 65
“First, what is the functional role of the IL-23 pathway gene variants associated with psoriasis? Second, is there any correlation between these genetic variants and disease phenotype? Third, are the newly discovered genetic variants of any use in pharmacogenetic studies to predict treatment response? Moreover, a recen…”
BackgroundRelvas, M., & Torres, T. R. (2017) · American Journal of Clinical Dermatology · doi:10.1007/s40257-017-0294-9 · Cited by 64
“In the same study, anti-streptolysin O levels correlated with up-regulation of messenger RNA for three of those four mediators, IL-17, IL-22, and interferonc, plus IP-10, a potent chemokine expressed in psoriatic lesions [29].”
BackgroundAllergies – A T cells perspective in the era beyond the TH1/TH2 paradigm
Berker, M., Frank, L. J., Geßner, A. L., Graßl, N., Holtermann, A., Höppner, S., Kraef, C., Leclaire, M. D., Maier, P., Messerer, D. A. C., et al. (2016) · Clinical Immunology · doi:10.1016/j.clim.2016.11.001 · Cited by 67
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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