Neutrophil recruitment by CD4 tissue-resident memory T cells induces chronic recurrent inflammation in atopic dermatitis

被引:9
作者
Zheng, Chunjiao [1 ]
Cao, Ting [1 ]
Ye, Chengbin [1 ]
Zou, Ying [1 ]
机构
[1] Tongji Univ, Shanghai Skin Dis Hosp, Skin & Cosmet Res Dept, Sch Med, Shanghai, Peoples R China
基金
中国国家自然科学基金;
关键词
Tissue-resident memory T cell; Atopic dermatitis; Neutrophil; CXCL1; THYMIC STROMAL LYMPHOPOIETIN; TRM CELLS; TRIGGER; FTY720;
D O I
10.1016/j.clim.2023.109805
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease that continues to impose significant physical, mental, and economic burdens on patients. Recent research has suggested the significant role of tissueresident memory (TRM) cells in AD. However, the precise role and mechanisms of action of TRM cells in AD remain unclear. A deeper understanding of the involvement of TRM cells in AD will unveil promising pathways for future innovative therapeutic strategies. Methods: To investigate the involvement of TRM cells in AD, we used diverse mouse models and employed experimental techniques to manipulate cell formation and depletion. We assessed the inflammatory response by analyzing mouse ear phenotype, measuring ear thickness, and performing hematoxylin and eosin staining. Flow cytometry and immunofluorescence staining were used to identify different cell types and evaluate changes in cell quantity. Additionally, we used qPCR to analyze gene expression of relevant chemokines and cytokines. Results: Our study revealed the presence of TRM cells in the skin after exposure to calcipotriol. After a 24-h rechallenge, we observed substantial neutrophil infiltration into the previously irritated skin. Neutrophil depletion prior to re-challenge effectively prevented early flare-up responses during AD recurrence. Furthermore, we demonstrate that CD4+TRM cells upregulate expression of cytokines INF-gamma and TNF-alpha, which may induce the expression of CXCL1, thereby recruiting neutrophils and contributing to the chronic recurrent inflammation observed in AD. Conclusions: We have established a novel, chronic recurrent mouse model for investigating TRM cells in AD. Our findings demonstrate that CD4+TRM cells in the skin mediate early flare-up response during AD recurrence and influence the chronic recurrent inflammation of AD by recruiting neutrophils. Targeting CD4+TRM cells may represent a promising approach for the treatment of chronic recurrent inflammation in AD.
引用
收藏
页数:10
相关论文
共 33 条
  • [21] Multicytokine-producing tissue resident memory (TRM) cells in atopic dermatitis patient
    Kim, S.
    Park, C.
    Shin, J.
    Noh, J.
    Kim, H.
    Kim, J.
    Lee, H.
    Lee, J.
    Kupper, T. S.
    Lee, K.
    [J]. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2016, 136 (05) : S9 - S9
  • [22] Langan SM, 2020, LANCET, V396, P345, DOI 10.1016/S0140-6736(20)31286-1
  • [23] Topical vitamin D3 and low-calcemic analogs induce thymic stromal lymphopoietin in mouse keratinocytes and trigger an atopic dermatitis
    Li, Mei
    Hener, Pierre
    Zhang, Zhikun
    Kato, Shigeaki
    Metzger, Daniel
    Chambon, Pierre
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (31) : 11736 - 11741
  • [24] What's new in atopic eczema? An analysis of systematic reviews published in 2016. Part 2: Epidemiology, aetiology and risk factors
    Lloyd-Lavery, A.
    Solman, L.
    Grindlay, D. J. C.
    Rogers, N. K.
    Thomas, K. S.
    Harman, K. E.
    [J]. CLINICAL AND EXPERIMENTAL DERMATOLOGY, 2019, 44 (04) : 370 - 375
  • [25] Tissue-Resident T Cells and Other Resident Leukocytes
    Masopust, David
    Soerens, Andrew G.
    [J]. ANNUAL REVIEW OF IMMUNOLOGY, VOL 37, 2019, 2019, 37 : 521 - 546
  • [26] Eosinophils Determine Dermal Thickening and Water Loss in an MC903 Model of Atopic Dermatitis
    Naidoo, Karmella
    Jagot, Ferdinand
    van den Elsen, Lieke
    Pellefigues, Christophe
    Jones, Angela
    Luo, Huijun
    Johnston, Karen
    Painter, Gavin
    Roediger, Ben
    Lee, James
    Weninger, Wolfgang
    Le Gros, Graham
    Forbes-Blom, Elizabeth
    [J]. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2018, 138 (12) : 2606 - 2616
  • [27] Exposure to food allergens through inflamed skin promotes intestinal food allergy through the thymic stromal lymphopoietin-basophil axis
    Noti, Mario
    Kim, Brian S.
    Siracusa, Mark C.
    Rak, Gregory D.
    Kubo, Masato
    Moghaddam, Amin E.
    Sattentau, Quentin A.
    Comeau, Michael R.
    Spergel, Jonathan M.
    Artis, David
    [J]. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2014, 133 (05) : 1390 - U643
  • [28] Tissue-Resident Memory T Cells
    Schenkel, Jason M.
    Masopust, David
    [J]. IMMUNITY, 2014, 41 (06) : 886 - 897
  • [29] Resident memory CD8 T cells trigger protective innate and adaptive immune responses
    Schenkel, Jason M.
    Fraser, Kathryn A.
    Beura, Lalit K.
    Pauken, Kristen E.
    Vezys, Vaiva
    Masopust, David
    [J]. SCIENCE, 2014, 346 (6205) : 98 - 101
  • [30] Rapid allergen-induced interleukin-17 and interferon-γ secretion by skin-resident memory CD8+ T cells
    Schmidt, Jonas D.
    Ahlstrom, Malin G.
    Johansen, Jeanne D.
    Dyring-Andersen, Beatrice
    Agerbeck, Christina
    Nielsen, Morten M.
    Poulsen, Steen S.
    Woetmann, Anders
    Odum, Niels
    Thomsen, Allan R.
    Geisler, Carsten
    Bonefeld, Charlotte M.
    [J]. CONTACT DERMATITIS, 2017, 76 (04) : 218 - 227