Stanley Cheuk

MRC Weatherall Institute of Molecular Medicine

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Liv Eidsmo

Karolinska Institutet

Elisa Martini

Vita-Salute San Raffaele University

Irène Gallais Sérézal

Centre Hospitalier Universitaire de Besançon

Georg A. Holländer

University Children’s Hospital Basel

Mona Ståhle

Karolinska Institutet

Andrea Introini

Karolinska University Hospital

Adam E. Handel

University of Oxford

Annelie Tjernlund

Karolinska University Hospital

Anna Gibbs

Karolinska University Hospital

David Chang

Karolinska Institutet

Cooperative Institutions

Karolinska Institutet

Karolinska University Hospital

University of Oxford

Medical University of Vienna

Rockefeller University

University of Massachusetts Chan Medical School

Johns Hopkins University

MRC Weatherall Institute of Molecular Medicine

Comprehensive Cancer Center Vienna

University of Amsterdam

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Composition of Innate Lymphoid Cell Subsets in the Human Skin: Enrichment of NCR + ILC3 in Lesional Skin and Blood of Psoriasis Patients

Journal of Investigative Dermatology (2014)

Marcel B. M. Teunissen J. Marius Munneke Jochem H. Bernink Phyllis I. Spuls Pieter C.M.

Innate lymphoid cell

10.1038/jid.2014.146

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Citations (299)

The Skinny on Fat Trm Cells

Immunity (2017)

Stanley Cheuk Liv Eidsmo

10.1016/j.immuni.2017.12.003

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Citations (3)

Dynamic Changes in Resident and Infiltrating Epidermal Dendritic Cells in Active and Resolved Psoriasis

Journal of Investigative Dermatology (2016)

Elisa Martini Maria Wikén Stanley Cheuk Irène Gallais Sérézal Faezzah Baharom

Epidermal Langerhans cells (LCs) are spatially separated from dermal dendritic cells (DCs) in healthy human skin. In active psoriasis, maintained by local production of IL-23 and IL-17, inflammatory DCs infiltrate both skin compartments. Here we show that CCR2+ epidermal DCs (eDCs) were confined to lesional psoriasis and phenotypically distinct from dermal DCs. The eDCs exceeded the number of LCs and displayed high expression of genes involved in neutrophil recruitment and the activation of keratinocytes and T cells. Resident LCs responded to toll-like receptor 4 and toll-like receptor 7/8 activation with increased IL-23 production, whereas eDCs additionally produced IL-1β together with IL-23 and tumor necrosis factor. Psoriasis typically recur in fixed skin lesions. eDCs were absent from resolved psoriasis. Instead, LCs from anti-tumor necrosis factor-treated lesions retained high IL23A expression and responded to toll-like receptor stimulation by producing IL-23. Our results reveal phenotypic and functional properties of eDCs and resident LCs in different clinical phases of psoriasis, and the capacity of these cells to amplify the epidermal microenvironment through the secretion of IL-17 polarizing cytokines.

Proinflammatory cytokine

10.1016/j.jid.2016.11.033

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Citations (69)

CD49a Expression Defines Tissue-Resident CD8 + T Cells Poised for Cytotoxic Function in Human Skin

Immunity (2017)

Stanley Cheuk Heinrich Schlums Irène Gallais Sérézal Elisa Martini Samuel C. C. Chiang

Tissue-resident memory T (Trm) cells form a heterogeneous population that provides localized protection against pathogens. Here, we identify CD49a as a marker that differentiates CD8+ Trm cells on a compartmental and functional basis. In human skin epithelia, CD8+CD49a+ Trm cells produced interferon-γ, whereas CD8+CD49a− Trm cells produced interleukin-17 (IL-17). In addition, CD8+CD49a+ Trm cells from healthy skin rapidly induced the expression of the effector molecules perforin and granzyme B when stimulated with IL-15, thereby promoting a strong cytotoxic response. In skin from patients with vitiligo, where melanocytes are eradicated locally, CD8+CD49a+ Trm cells that constitutively expressed perforin and granzyme B accumulated both in the epidermis and dermis. Conversely, CD8+CD49a– Trm cells from psoriasis lesions predominantly generated IL-17 responses that promote local inflammation in this skin disease. Overall, CD49a expression delineates CD8+ Trm cell specialization in human epithelial barriers and correlates with the effector cell balance found in distinct inflammatory skin diseases.

Expression (computer science)

10.1016/j.immuni.2017.01.009

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Citations (516)

Cellular scars and local crosstalk in relapsing psoriasis: an example of a skin sticking disease

Scandinavian Journal of Immunology (2020)

Irène Gallais Sérézal Stanley Cheuk Elisa Martini Liv Eidsmo

Psoriasis is an inflammatory disease that arises in genetically predisposed individuals. Chronic skin lesions that contain activated immune cells can persist for years. Systemic inhibition of TNF, IL-17 and IL-23 cytokines has revolutionized psoriasis care during the recent decades. Unfortunately, local relapse of disease is common at previously inflamed sites after cessation of treatment. This highlights that fundamental pathologic alterations of the affected tissues are not completely resolved during clinical remission. Here, we present arguments for a local disease memory located in both dermis and epidermis in psoriasis skin. We decipher different cellular components and intercellular crosstalk that sustain local disease memory and amplify disease relapse in human psoriasis. Decrypting the mechanisms underlying the establishment and persistence of pathogenic memory cells in resolved psoriasis may provide new therapeutic perspectives aimed at long-term remission of psoriasis.

Crosstalk

10.1111/sji.12953

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Citations (9)

Developmental dynamics of the neural crest–mesenchymal axis in creating the thymic microenvironment

Science Advances (2022)

Adam E. Handel Stanley Cheuk Fatima Dhalla Stefano Maio Tania Hübscher

The thymic stroma is composed of epithelial and nonepithelial cells providing separate microenvironments controlling homing, differentiation, and selection of hematopoietic precursor cells to functional T cells. Here, we explore at single-cell resolution the complex composition and dynamic changes of the nonepithelial stromal compartment across different developmental stages in the human and mouse thymus, and in an experimental model of the DiGeorge syndrome, the most common form of human thymic hypoplasia. The detected gene expression signatures identify previously unknown stromal subtypes and relate their individual molecular profiles to separate differentiation trajectories and functions, revealing an unprecedented heterogeneity of different cell types that emerge at discrete developmental stages and vary in their expression of key regulatory signaling circuits and extracellular matrix components. Together, these findings highlight the dynamic complexity of the nonepithelial thymus stroma and link this to separate instructive roles essential for normal thymus organogenesis and tissue maintenance.

Organogenesis

Homing (biology)

Compartment (ship)

Developmental Biology

DiGeorge syndrome

Cell type

Crosstalk

10.1126/sciadv.abm9844

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Citations (11)

Genetic Variants of the IL22 Promoter Associate to Onset of Psoriasis before Puberty and Increased IL-22 Production in T Cells

Journal of Investigative Dermatology (2014)

Pernilla Nikamo Stanley Cheuk Josefin Lysell Charlotta Enerbäck Kerstin Bergh

Interleukin 22

Genome-wide Association Study

10.1038/jid.2014.5

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Citations (42)

Human Immunodeficiency Virus-Infected Women Have High Numbers of CD103−CD8+ T Cells Residing Close to the Basal Membrane of the Ectocervical Epithelium

The Journal of Infectious Diseases (2017)

Anna Gibbs Marcus Buggert Gabriella Edfeldt Petter Ranefall Andrea Introini

Genital mucosa is the main portal of entry for various incoming pathogens, including human immunodeficiency virus (HIV), hence it is an important site for host immune defenses. Tissue-resident memory T (TRM) cells defend tissue barriers against infections and are characterized by expression of CD103 and CD69. In this study, we describe the composition of CD8+ TRM cells in the ectocervix of healthy and HIV-infected women. Study samples were collected from healthy Swedish and Kenyan HIV-infected and uninfected women. Customized computerized image-based in situ analysis was developed to assess the ectocervical biopsies. Genital mucosa and blood samples were assessed by flow cytometry. Although the ectocervical epithelium of healthy women was populated with bona fide CD8+ TRM cells (CD103+CD69+), women infected with HIV displayed a high frequency of CD103−CD8+ cells residing close to their epithelial basal membrane. Accumulation of CD103−CD8+ cells was associated with chemokine expression in the ectocervix and HIV viral load. CD103+CD8+ and CD103−CD8+ T cells expressed cytotoxic effector molecules in the ectocervical epithelium of healthy and HIV-infected women. In addition, women infected with HIV had decreased frequencies of circulating CD103+CD8+ T cells. Our data provide insight into the distribution of CD8+ TRM cells in human genital mucosa, a critically important location for immune defense against pathogens, including HIV.

10.1093/infdis/jix661

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Citations (17)

FOXN1 forms higher-order nuclear condensates displaced by mutations causing immunodeficiency

Science Advances (2021)

Ioanna A. Rota Adam E. Handel Stefano Maio Fabian Klein Fatima Dhalla

A dominant transcription factor mutation disrupting nuclear liquid phase separation causes human immunodeficiency.

10.1126/sciadv.abj9247

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Citations (17)

413 Epithelial resident and infiltrating dendritic cells amplify active and resolved psoriasis inflammation

Journal of Investigative Dermatology (2016)