Welcome to Scholar Publishing Group

International Journal of World Medicine, 2023, 4(2); doi: 10.38007/IJWM.2023.040210.

Advances in Cellular Immune Mechanisms of Atopic Dermatitis


Jianghui Li, Xiaoning Yan, Haoyuan Hu

Corresponding Author:
Xiaoning Yan

Shaanxi Provincial Hospital of Chinese Medicine, Xi'an 710003, Shaanxi, China


Atopic dermatitis is a common chronic inflammatory skin disease with severe itching as the most obvious clinical symptom. Its immunological mechanism is very complex, involving the participation of multiple immune cells and their cytokines, chemokines, pro-inflammatory molecules and other immune cascades. At the same time, it is related to skin barrier destruction, decreased expression of antimicrobial peptides, and immune-nervous system crosstalk. This article mainly reviews the various cells, cytokines and their cascades in the immune-related pathogenesis of atopic dermatitis, in order to provide corresponding theoretical basis for the treatment of atopic dermatitis.


Atopic Dermatitis, Immune Mechanism, Inflammation, Cytokines

Cite This Paper

Jianghui Li, Xiaoning Yan, Haoyuan Hu. Advances in Cellular Immune Mechanisms of Atopic Dermatitis. International Journal of World Medicine (2023), Vol. 4, Issue 2: 81-92. https://doi.org/10.38007/IJWM.2023.040210.


[1] Yun Yang.Clinical manifestations and characteristics of atopic dermatitis in children.Journal of Medicine Forum,2022,43(07):16-19+23.

[2] Lu Huang,Caiyun Li,Yan Zhao.Association of atopic dermatitis with related autoimmune diseases.Journal of Clinical and Pathology,2022,42(6):1466-1471.

[3] Sinéad M Langan,Alan Owen,Stephen Weittinger.Atopic Dermatitis.Lancet,2020,396:345-360.

[4] Yuan Li,Lei Zheng,Dong Chen.To investigate the correlation between the levels of serum IgE, IFN-γ and Th17 cytokines and the severity of adult atopic dermatitis[J/OL].Journal of Wuhan University (Medical Edition),2022-12-02/2022-12-20.

[5] Stefano Piazza,Marco Fumagalli,Giulia Martinelli,et al.Hydrolyzable Tannins in the Management of Th1,Th2 and Th17 Inflammatory-Related Diseases.Molecules,2022,27(21):7593.

[6] Danso M O,van Drongelen V,Mulder A,et al.TNF-α and Th2 cytokines induce atopic dermatitis-like features on epidermal differentiation proteins and stratum corneum lipids in human skin equivalents. Investig Dermatol,2014,134(7),1941-1950.

[7] Tsuji G,Hashimoto-Hachiya A,Kiyomatsu-Oda M,et al.Aryl hydrocarbon receptor activation restores filaggrin expression via OVOL1 in atopic dermatitis[J/OL].Cell Death Dis,2017-07-13/2022-12-20.

[8] Thomas Bieber.Interleukin‐13: Targeting an underestimated cytokine in atopic Dermatitis.Allergy,2020,75(1):54-62.

[9] Xiao S,Lu Z,Steinhoff M,et al.Innate immune regulates cutaneous sensory IL-13 receptor alpha 2 to promote atopic dermatitis.Brain Behav Immun,2021,98:28-39.

[10] Furue M,Chiba T,Tsuji G,et al.Atopic dermatitis: immune deviation, barrier dysfunction, IgE autoreactivity and new therapies.Allergol Int.2017,66(3):398-403.

[11] Lee E,Min K,Ahn H,et al.Potential Therapeutic Skin Microbiomes Suppressing Staphylococcus aureus-Derived Immune Responses and Upregulating Skin Barrier Function-Related Genes via the AhR Signaling Pathway.Int J Mol Sci,2022,23(17):9551.

[12] Patrick M Brunner,Emma Guttman-Yassky,Donald Y M Leung.The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies.J Allergy Clin Immunol,2017,139(4):65-76.

[13] Tsuji G,Hashimoto-Hachiya A,Kiyomatsu-Oda M,et al.Aryl hydrocarbon receptor activation restores filaggrin expression via OVOL1 in atopic dermatitis. Cell Death Dis,2017,8:e2931.

[14] Kazuhisa Furue,Takamichi Ito,Gaku Tsuji,et al.The IL-13-OVOL1-FLG axis in atopic dermatitis.Immunology,2019,158(4):281-286. 

[15] Michael J Cork,Simon G Danby,Graham S Ogg.Atopic dermatitis epidemiology and unmet need in the United Kingdom.Journal of Dermatological Treatment, 2020,31(8):801-809.

[16] Borgia F,Custurone P,Li Pomi F,et al.IL-31: State of the Art for an Inflammation-Oriented Interleukin.Int J Mol Sci,2022,23(12):6507.

[17] Liyuan Liu,Xinsuo Duan.Research progress on immune-related pathogenesis of atopic dermatitis.Journal of Chengde Medical College,2022,39(3):247-251.

[18] Swindell W R,Bojanowski K,Chaudhuri R K.Isosorbide Fatty Acid Diesters Have Synergistic Anti-Inflammatory Effects in Cytokine-Induced Tissue Culture Models of Atopic Dermatitis.Int J Mol Sci,2022,23(22): 14307.

[19] Tsiogka A,Kyriazopoulou M,Kontochristopoulos G,et al.The JAK/STAT Pathway and Its Selective Inhibition in the Treatment of Atopic Dermatitis: A Systematic Review.J Clin Med,2022,11(15):4431.

[20] Lee H J,Hong Y J,Kim M.Angiogenesis in Chronic Inflammatory Skin Disorders.Int J Mol Sci,2021,22(21):12035.

[21] Eyerich K,Pennino D,Scarponi C,et al.IL-17 in atopic eczema: Linking allergen-specific adaptive and microbial-triggered innate immune response.J Allergy Clin Immunol,2009,123(1):59–66.

[22] Sugaya M.The Role of Th17-Related Cytokines in Atopic Dermatitis. Int J Mol Sci,2020,21(4):1314.

[23] Sahiner U M,Layhadi J A,Golebski K,et al.Innate lymphoid cells: The missing part of a puzzle in food allergy.Allergy,2021,76(7):2002-2016.

[24] Packi K,Matysiak J,Klimczak S,et al.Analysis of the Serum Profile of Cytokines Involved in the T-Helper Cell Type 17 Immune Response Pathway in Atopic Children with Food Allergy.Int J Environ Res Public Health, 2022,19(13):7877. 

[25] Julia Borowczyk,Maria Shutova,Nicolo Costantino Brembilla,et al.IL-25 (IL-17E) in epithelial immunology and pathophysiology.J Allergy Clin Immunol,2021,148(1):40-52.

[26] Hvid M,Vestergaard C,Kemp K,et al.IL-25 in atopic dermatitis: a possible link between inflammation and skin barrier dysfunction?.J Invest Dermatol,2011,131(1): 150-157.

[27] Aktar M K,Kido-Nakahara M,Furue M,et al.Mutual upregulation of endothelin-1 and IL-25 in atopic dermatitis.Allergy,2015,70(7): 846-854

[28] SiHang Wang,YaGang Zuo.Mechanism and clinical application of thymic stromal lymphopoietin in atopic dermatitis.Chinese Journal of Allergy and Clinical Immunology,2022,16(1):66-71.

[29] Zhi Li,Tingting Yang,WenZhe Li.Expression of Th22, Treg cells and their cytokines in peripheral blood of patients with atopic dermatitis.Chinese Journal of Laboratory Diagnosis ,2019,23(5):788-791.

[30] Zhang D J,Hao F,Qian T,et al.Expression of Helper and Regulatory T Cells in Atopic Dermatitis:A Meta-Analysis.Front Pediatr,2022, 10:777992.

[31] Masutaka Furue,Takahito Chiba,Gaku Tsuji,et al.Atopic dermatitis:immune deviation,barrier dysfunction,IgE autoreactivity and new therapies.Allergology International,2017,66(3):398-403.

[32] Gittler J K,Shemer A,M Suarez-Farinas,et al.Progressive activation of T2/T22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis.J Allergy Clin Immunol,2012, 130, 1344.

[33] Hongfei Lou,Jingning Lu,Eun Byul Choi,et al.Expression of IL-22 in the Skin Causes Th2-Biased Immunity,Epidermal Barrier Dysfunction, and Pruritus via Stimulating Epithelial Th2 Cytokines and the GRP Pathway.J Immunol,2017,198 (7): 2543-2555.

[34] Fukaya T,Fukui T,Uto T,et al.Pivotal role of il-22 Binding Protein in the epithelial autoregulation of interleukin-22 signaling in the control of skin inflammation.Front Immunol,2018,9:1418. 

[35] Masutaka Furue.Regulation of Filaggrin, Loricrin, and Involucrin by IL-4, IL-13, IL-17A, IL-22, AHR, and NRF2: Pathogenic Implications in Atopic Dermatitis.Int J Mol Sci,2020,21(15):5382.

[36] Lopez,DV,Kongsbak-Wismann M.Role of IL-22 in homeostasis and diseases of the skin.APMIS,2022,130(6): 314-322.

[37] Yuting Xu,Qun Hu.Research progress of neutrophil dysfunction.Journal of China Pediatric Blood and Cancer,2021,26(1):51-55.

[38] David F Choy,Daniel K Hsu,Dhaya Seshasayee,et al.Comparative transcriptomic analyses of atopic dermatitis and psoriasis reveal shared neutrophilic inflammation.J Allergy Clin Immunol,2012,130(6):1335-1343.

[39] A Schabitz,K Eyerich,N Garzorz-Stark.So close, and yet so far away: The dichotomy of the specific immune response and inflammation in psoriasis and atopic dermatitis.Journal of Internal Medicine,2021, 290:27–39.

[40] Hashimoto,T Rosen,J D Sanders,et al.Possible role of neutrophils in itch.J Itch,2018,3:e17.

[41] Carolyn M Walsh,Rose Z Hill,Jamie Schwendinger-Schreck,et al.Neutrophils promote CXCR3-dependent itch in the development of atopic dermatitis[J/OL].eLife,2019-10-21/2022-12-20.

[42] Cunha T M,Waldiceu A Verri,Ieda R Schivo,et al.Crucial role of neutrophils in the development of mechanical inflammatory hypernociception.J Leukoc Biol,2008,83(4):824-832.

[43] Wagner K M,Gomes A,McReynolds C B.Soluble epoxide hydrolase regulation of lipid mediators limits pain.Neurotherapeutics,2020,17(3): 900-916.

[44] Sadik C D,Kim N D,Luster A D.Neutrophils cascading their way to inflammation.Trends Immunol,2011,32(10): 452-460.

[45] Janine Woytschak,Nadia Keller,Carsten Krieg,et al.Type 2 Interleukin-4 Receptor Signaling in Neutrophils Antagonizes Their Expansion and Migration during Infection and Inflammation.Immunity,2016,45(1):172-184.

[46] D Simon,L R Braathen,H U Simon.Eosinophils and atopic dermatitis.Allergy,2004,59(6):561-570.

[47] Weller P F,Spencer L A.Functions of tissue-resident eosinophils.Nat Rev Immunol,2017,17(12):746-760.

[48] Inokuchi-Sakata S,Ishiuji Y,Katsuta M,et al.Role of Eosinophil Relative Count and Neutrophil-to-Lymphocyte Ratio in the Assessment of Severity of Atopic Dermatitis[J/OL].Acta Dermato-Venereologica,2021-07-07/2022-12-20.

[49] Raap U,Goltz C,Deneka N,et al.Brain-derived neurotrophic factor is increased in atopic dermatitis and modulates eosinophil functions compared with that seen in nonatopic subjects.J Allergy Clin Immunol, 2005,115(6):1268-1275.

[50] Kunsleben N,Rudrich U,Gehring M,et al.IL-31 Induces chemotaxis, calcium mobilization, release of reactive oxygen species, and CCL26 in eosinophils, which are capable to release IL-31.J Invest Dermatol,2015,135(7): 1908-1911.

[51] Beyer L,Kabatas A S,Mommert S,et al.Histamine Activates Human Eosinophils via H2R and H4R Predominantly in Atopic Dermatitis Patients.Int J Mol Sci,2022,23(18):10294.

[52] Sandersa N L,V enkateshaiah S U, Manohar M.Interleukin-18 has an ImportantRole in Differentiation and Maturation of Mucosal Mast Cells. J Mucosal Immunol Res,2018,2(1):109.

[53] Yousefi S,Gold J A,Andina N,et al.Catapult-like release of mitochondrial DNA by eosinophils contributes to antibacterial defense.Nat Med,2008,14:949-953.

[54] Morshed M,Yousefi S,Stockle C,et al.Thymic stromal lymphopoietin stimulates the formation of eosinophil extracellular traps.Allergy 2012,67:1127-1137.