Psoriasis-associated impairment of CCL27/CCR10-derived regulation leads to IL-17A/IL-22–producing skin T-cell overactivation

Li, Chao; Xu, Ming; Coyne, James; Wang, Wei Bei; Davila, Micha L.; Wang, Yong; Xiong, Na

doi:10.1016/j.jaci.2020.05.044

Cited by 18 publications

(20 citation statements)

References 26 publications

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“…CCR10 has also been described as a common marker on regulatory CD4+ T cells ( 44 ). Loss of CCR10 in murine models results in loss of Treg cells in skin, which enhances IL‐17A and tumor necrosis factor production at the cost of IL‐10 production ( 25 , 45 , 46 ). This indicates that CCR10 is important for the regulatory function of tissue‐resident T cells in noninflamed murine skin ( 25 , 46 ).…”

Section: Discussionmentioning

confidence: 99%

“…Loss of CCR10 in murine models results in loss of Treg cells in skin, which enhances IL‐17A and tumor necrosis factor production at the cost of IL‐10 production ( 25 , 45 , 46 ). This indicates that CCR10 is important for the regulatory function of tissue‐resident T cells in noninflamed murine skin ( 25 , 46 ). Overall, the transcriptomic profile and functional assays performed in our study indicate that these cells could have an important regulatory function in human skin.…”

Section: Discussionmentioning

confidence: 99%

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Tissue‐Resident Memory CD8+ T Cells From Skin Differentiate Psoriatic Arthritis From Psoriasis

Leijten

Kempen

Nordkamp

et al. 2021

Arthritis & Rheumatology

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Objective To compare immune cell phenotype and function in psoriatic arthritis (PsA) versus psoriasis in order to better understand the pathogenesis of PsA. Methods In‐depth immunophenotyping of different T cell and dendritic cell subsets was performed in patients with PsA, psoriasis, or axial spondyloarthritis and healthy controls. Subsequently, we analyzed cells from peripheral blood, synovial fluid (SF), and skin biopsy specimens using flow cytometry, along with high‐throughput transcriptome analyses and functional assays on the specific cell populations that appeared to differentiate PsA from psoriasis. Results Compared to healthy controls, the peripheral blood of patients with PsA was characterized by an increase in regulatory CD4+ T cells and interleukin‐17A (IL‐17A) and IL‐22 coproducing CD8+ T cells. One population specifically differentiated PsA from psoriasis: i.e., CD8+CCR10+ T cells were enriched in PsA. CD8+CCR10+ T cells expressed high levels of DNAX accessory molecule 1 and were effector memory cells that coexpressed skin‐homing receptors CCR4 and cutaneous lymphocyte antigen. CD8+CCR10+ T cells were detected under inflammatory and homeostatic conditions in skin, but were not enriched in SF. Gene profiling further revealed that CD8+CCR10+ T cells expressed GATA3, FOXP3, and core transcriptional signature of tissue‐resident memory T cells, including CD103. Specific genes, including RORC, IFNAR1, and ERAP1, were up‐regulated in PsA compared to psoriasis. CD8+CCR10+ T cells were endowed with a Tc2/22‐like cytokine profile, lacked cytotoxic potential, and displayed overall regulatory function. Conclusion Tissue‐resident memory CD8+ T cells derived from the skin are enhanced in the circulation of patients with PsA compared to patients with psoriasis alone. This may indicate that aberrances in cutaneous tissue homeostasis contribute to arthritis development.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Tissue‐Resident Memory CD8+ T Cells From Skin Differentiate Psoriatic Arthritis From Psoriasis

Leijten

Kempen

Nordkamp

et al. 2021

Arthritis & Rheumatology

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“…CTACK/CCL27 is a skin‐specific chemokine, and together with its receptor CCR10, has been considered to have roles in induction of skin inflammation including psoriasis 1 . However, recent findings revealed its suppressive roles in psoriasis inflammation, which contradicts the previous hypothesis 2 . Our previous investigation revealed the existence of CTACK/CCL27 in the whole epidermis in perilesional skin, while it is restricted to the basal layer in the lesional epidermis, with clearly demarcated borders 3 .…”

Section: Figurementioning

confidence: 63%

“…Our previous report demonstrated that CTACK/CCL27 stained in the whole epidermis in the normal looking area surrounding the lesion (perilesion), while its expression was limited to the basal layer in the lesional epidermis of psoriasis 3 . Recent findings demonstrated that CTACK/CCL27 has a suppressive role in psoriasis inflammation 2 . We speculate that CTACK/CCL27 may be important in initial lymphocyte infiltration in skin inflammation, including psoriasis, but it also has a suppressing effect in the late stage of psoriasis lesion formation.…”

Section: Figurementioning

confidence: 97%

Calcipotriol induces the production of CTACK/CCL27, one of the potential suppressive factors in psoriasis inflammation

Karakawa

Kishimoto

Ohtsuki

et al. 2021

The Journal of Dermatology

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“…As such, MNAs can be used for effective and reproducible delivery of a myriad of bioactive molecules for different applications, such as in the treatment of cutaneous diseases (e.g., acne vulgaris, alopecia, and psoriasis), intracutaneous vaccination, management of diabetes, and immunotherapy for skin cancer (Amani et al, 2021;Kim et al, 2020;Korkmaz et al, 2015;Moreira et al, 2019;Wang et al, 2016;Yang et al, 2021Yang et al, , 2019Yu et al, 2015;Zhang et al, 2018). MNA delivery of biologics, such as mAbs, extracellular vesicles, chemokines, and CRISPR-Cas9-based therapeutics, holds great potential for effective treatment of cutaneous disorders, such as psoriasis, alopecia, and atopic dermatitis, as well as of skin cancer (Korkmaz et al, 2015;Li et al, 2021;Wan et al, 2021;Wang et al, 2016;Yang et al, 2019).…”

Section: Dissolving Mna-directed Drug Deliverymentioning

confidence: 99%

Research Techniques Made Simple: Skin-Targeted Drug and Vaccine Delivery Using Dissolvable Microneedle Arrays

Balmert

Ghozloujeh

Carey

et al. 2021

Journal of Investigative Dermatology

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Skin-targeted drug delivery is broadly employed for both local and systemic therapeutics and is an important tool for discovery efforts in cutaneous biology. Recently, emerging technologies support efforts toward skintargeted biocargo delivery for local and systemic therapeutic benefit. Effective targeting of bioactive molecules, including large (molecular weight > 500 Da) or complex (hydrophilic and charged) molecules, to defined cutaneous microenvironments is intrinsically challenging owing to the protective barrier function of the skin. Dissolvable microneedle arrays (MNAs) have proven to be a promising technology to address the unmet need for controlled, minimally invasive, and reliable delivery of a wide range of biocargos to the skin. In this paper, we describe the unique properties of the skin that make it an attractive target for vaccine delivery, for immunemodulating therapies, and for systemic drug delivery and the structural characteristics of the skin that present obstacles to efficient intracutaneous and transdermal delivery of bioactive molecules. We provide an overview of MNA fabrication and the characteristics and mechanisms of dissolvable MNA cargo delivery to the cutaneous microenvironment. We present a representative example of a clinical application of MNAs and discuss future directions for MNA development and applications.

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Psoriasis-associated impairment of CCL27/CCR10-derived regulation leads to IL-17A/IL-22–producing skin T-cell overactivation

Cited by 18 publications

References 26 publications

Tissue‐Resident Memory CD8+ T Cells From Skin Differentiate Psoriatic Arthritis From Psoriasis

Tissue‐Resident Memory CD8+ T Cells From Skin Differentiate Psoriatic Arthritis From Psoriasis

Calcipotriol induces the production of CTACK/CCL27, one of the potential suppressive factors in psoriasis inflammation

Research Techniques Made Simple: Skin-Targeted Drug and Vaccine Delivery Using Dissolvable Microneedle Arrays

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