T‐cell receptor sequencing specifies psoriasis as a systemic and atopic dermatitis as a skin‐focused, allergen‐driven disease

Roesner, Lennart M.; Farag, Ahmed K.; Pospich, Rebecca; Traidl, Stephan; Werfel, Thomas

doi:10.1111/all.15272

Cited by 15 publications

(25 citation statements)

References 63 publications

(110 reference statements)

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“…Interestingly it has recently been reported that an early-term effect of dupilumab treatment on IL-13, IL-4, IL-5 and IL-22 expression is preferentially found in circulating CD4 + CLA + T cells from AD patients ( 62 , 63 ). Besides this, circulating allergen-specific and CLA + T cells share the same TCRB CDR3 regions as lesional T cells from AD skin ( 64 ), supporting the relevance of our results for IL-31 produced by peripheral skin-homing T cells.…”

Section: Discussionsupporting

confidence: 84%

Allergen sensitization stratifies IL-31 production by memory T cells in atopic dermatitis patients

et al. 2023

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BackgroundThe role of allergen sensitization in IL-31 production by T cells and specifically in the clinical context of atopic dermatitis (AD) has not been characterized.MethodsThe response to house dust mite (HDM) in purified memory T cells cocultured with epidermal cells from AD patients (n=58) and control subjects (n=11) was evaluated. AD-associated cytokines from culture supernatants, plasma proteins and mRNA expression from cutaneous lesions were assessed and related with the clinical features of the patients.ResultsHDM-induced IL-31 production by memory T cells defined two subsets of AD patients according to the presence or absence of IL-31 response. Patients in the IL-31 producing group showed a more inflammatory profile, and increased HDM-specific (sp) and total IgE levels compared to the IL-31 non-producing group. A correlation between IL-31 production and patient’s pruritus intensity, plasma CCL27 and periostin was detected. When the same patients were analyzed based on sp IgE and total IgE levels, an increased IL-31 in vitro response, as well as type 2 markers in plasma and cutaneous lesions, was found in patients with sp IgE levels > 100 kUA/L and total IgE levels > 1000 kU/L. The IL-31 response by memory T cells was restricted to the cutaneous lymphocyte-associated antigen (CLA)+ T-cell subset.ConclusionIgE sensitization to HDM allows stratifying IL-31 production by memory T cells in AD patients and relating it to particular clinical phenotypes of the disease.

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Section: Discussionsupporting

confidence: 84%

Allergen sensitization stratifies IL-31 production by memory T cells in atopic dermatitis patients

et al. 2023

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“…Propagated T-cell clones in AD and PS lesional skin have been reported to be detectable in clonalities of about 1%-10%. 19,53 In our set of data, we observed the highest levels of clonal expansion of T cells in the disease-specific cell clusters in lesional skin, indicating that these cells respond to disease-driving antigens. This effect was robust among the AD Th2/ Th22 as well as PS Th17/Tc17 cell clusters and implies that antigenrecognition is causative for the development of these clusters.…”

Section: Discussionmentioning

confidence: 63%

“…19 Furthermore, these bona fide disease-driving T cells are also detectable within circulating PBMC as so-called skin-homing T cells. 19 The sequencing approach applied here allows detection of clonally propagated T cells and phenotyping in parallel.…”

Section: Sctcr-seq Profiling Of Skin and Pbmcs Reveals Expanded And P...mentioning

confidence: 99%

Single‐cell profiles reveal distinctive immune response in atopic dermatitis in contrast to psoriasis

Zhang

Roesner

Traidl

et al. 2022

Allergy

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Background Understanding the complex orchestrated inflammation in atopic dermatitis (AD), one of the most common chronic inflammatory diseases worldwide, is essential for therapeutic approaches. However, a comparative analysis on the single‐cell level of the inflammation signatures correlated with the severity is missing so far. Methods We applied single‐cell RNA and T‐cell receptor (TCR) sequencing on immune cells enriched from skin biopsies and matched blood samples of AD in comparison with psoriasis (PS) patients. Results Clonally propagated skin‐derived T cells showed disease‐specific TCR motifs shared between patients which was more pronounced in PS compared to AD. The disease‐specific T‐cell clusters were mostly of a Th2/Th22 sub‐population in AD and Th17/Tc17 in PS, and their numbers were associated with severity scores in both diseases. Herein, we provide for the first time a list that associates cell type‐specific gene expression with the severity of the two most common chronic inflammatory skin diseases. Investigating the cell signatures in the patients´ PBMCs and skin stromal cells, a systemic involvement of type‐3 inflammation was clearly detectable in PS circulating cells, while in AD inflammatory signatures were most pronounced in fibroblasts, pericytes, and keratinocytes. Compositional and functional analyses of myeloid cells revealed the activation of antiviral responses in macrophages in association with disease severity in both diseases. Conclusion Different disease‐driving cell types and subtypes which contribute to the hallmarks of type‐2 and type‐3 inflammatory signatures and are associated with disease activities could be identified by single‐cell RNA‐seq and TCR‐seq in AD and PS.

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“…The identification and characterization of allergen-specific T cells, their TCR sequences, and their reactive epitopes is critical for our ability to better treat patients with allergies (145). Studies on various tissue compartments and blood have broadly shown skewing of T cell repertoire usage with allergic disease (165)(166)(167)(168)(169). More targeted studies have examined the TCR repertoires and transcriptional profiles of antigen-specific T cells.…”

Section: Autoimmunity and Allergymentioning

confidence: 99%

Antigen-specificity measurements are the key to understanding T cell responses

et al. 2023

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Antigen-specific T cells play a central role in the adaptive immune response and come in a wide range of phenotypes. T cell receptors (TCRs) mediate the antigen-specificities found in T cells. Importantly, high-throughput TCR sequencing provides a fingerprint which allows tracking of specific T cells and their clonal expansion in response to particular antigens. As a result, many studies have leveraged TCR sequencing in an attempt to elucidate the role of antigen-specific T cells in various contexts. Here, we discuss the published approaches to studying antigen-specific T cells and their specific TCR repertoire. Further, we discuss how these methods have been applied to study the TCR repertoire in various diseases in order to characterize the antigen-specific T cells involved in the immune control of disease.

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T‐cell receptor sequencing specifies psoriasis as a systemic and atopic dermatitis as a skin‐focused, allergen‐driven disease

Cited by 15 publications

References 63 publications

Allergen sensitization stratifies IL-31 production by memory T cells in atopic dermatitis patients

Allergen sensitization stratifies IL-31 production by memory T cells in atopic dermatitis patients

Single‐cell profiles reveal distinctive immune response in atopic dermatitis in contrast to psoriasis

Antigen-specificity measurements are the key to understanding T cell responses

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