Desmoglein-Specific B-Cell−Targeted Single-Cell Analysis Revealing Unique Gene Regulation in Patients with Pemphigus

Egami, Shohei; Watanabe, Takashi; Fukushima-Nomura, Ayano; Nomura, Hisashi; Takahashi, Hayato; Yamagami, Jun; Ohara, Osamu; Amagai, Masayuki

doi:10.1016/j.jid.2023.03.1661

Cited by 6 publications

(3 citation statements)

References 52 publications

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“…Remarkably, the disease severity of PV has been correlated with the abundance of serum DSG1/3-specific autoantibody. The well-characterized antigenic specificity for DSG1/3 has allowed researchers to isolate these pathogenic B cells from the peripheral blood of PV patients, thus elucidating their distinctive transcriptomic and phenotypic profiles ( 51 – 53 ). Detection of DSG1/3-specific B cells in PV patients demonstrated that DSG1/3-specific memory B cells also correlate with disease severity ( 51 , 52 ).…”

Section: Role Of B Cells In Various Inflammatory Skin Diseasesmentioning

confidence: 99%

“…The well-characterized antigenic specificity for DSG1/3 has allowed researchers to isolate these pathogenic B cells from the peripheral blood of PV patients, thus elucidating their distinctive transcriptomic and phenotypic profiles ( 51 – 53 ). Detection of DSG1/3-specific B cells in PV patients demonstrated that DSG1/3-specific memory B cells also correlate with disease severity ( 51 , 52 ). Also, transcriptome analysis of autoreactive B cells performed at a single-cell level identified differentially expressed genes, encompassing those associated with T-cell costimulation ( CD137L ), B-cell differentiation ( CD9, BATF, TIMP-1 ), and proinflammatory cytokines ( S100A8, S100A9, CCL3 ) ( 51 ).…”

Section: Role Of B Cells In Various Inflammatory Skin Diseasesmentioning

confidence: 99%

“…Detection of DSG1/3-specific B cells in PV patients demonstrated that DSG1/3-specific memory B cells also correlate with disease severity ( 51 , 52 ). Also, transcriptome analysis of autoreactive B cells performed at a single-cell level identified differentially expressed genes, encompassing those associated with T-cell costimulation ( CD137L ), B-cell differentiation ( CD9, BATF, TIMP-1 ), and proinflammatory cytokines ( S100A8, S100A9, CCL3 ) ( 51 ).…”

Section: Role Of B Cells In Various Inflammatory Skin Diseasesmentioning

confidence: 99%

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From neglect to spotlight: the underappreciated role of B cells in cutaneous inflammatory diseases

Lee,

2024

Front. Immunol.

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The skin, covering our entire body as its largest organ, manifests enormous complexities and a profound interplay of systemic and local responses. In this heterogeneous domain, B cells were considered strangers. Yet, recent studies have highlighted their existence in the skin and their distinct role in modulating cutaneous immunity across various immune contexts. Accumulating evidence is progressively shedding light on the significance of B cells in maintaining skin health and in skin disorders. Herein, we integrate current insights on the systemic and local contributions of B cells in three prevalent inflammatory skin conditions: Pemphigus Vulgaris (PV), Systemic Lupus Erythematosus (SLE), and Atopic Dermatitis (AD), underscoring the previously underappreciated importance of B cells within skin immunity. Moreover, we address the potential adverse effects of current treatments used for skin diseases, emphasizing their unintentional consequences on B cells. These comprehensive approaches may pave the way for innovative therapeutic strategies that effectively address the intricate nature of skin disorders.

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Section: Role Of B Cells In Various Inflammatory Skin Diseasesmentioning

confidence: 99%

Section: Role Of B Cells In Various Inflammatory Skin Diseasesmentioning

confidence: 99%

Section: Role Of B Cells In Various Inflammatory Skin Diseasesmentioning

confidence: 99%

See 1 more Smart Citation

From neglect to spotlight: the underappreciated role of B cells in cutaneous inflammatory diseases

Lee,

2024

Front. Immunol.

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Immunostimulatory effects of Toll‐like receptor ligands as adjuvants in establishing a novel mouse model for pemphigus vulgaris

Gao,

Liu,

Xin

et al. 2024

Clinical & Translational Med

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BackgroundThe meticulous selection of appropriate vaccine adjuvants is crucial for optimizing immune responses. Traditionally, pemphigus vulgaris (PV), an autoimmune disorder, has been modelled using complete Freund's adjuvant (CFA). In this study, we aimed to discern potential variations in immune responses elicited by Toll‐like receptor (TLR) ligands as compared to CFA.MethodsA comprehensive investigation was conducted, comparing the effects of these adjuvants in conjunction with ovalbumin or desmoglein‐3. Flow cytometry was employed to analyse distinct cell subsets, while enzyme‐linked immunosorbent assay quantified antigen‐specific antibodies and cytokine levels. Histological examination of harvested skin tissues and transcriptome analysis of skin lesions were performed to identify differentially expressed genes.ResultsTLR ligands demonstrated efficacy in inducing PV‐like symptoms in wild‐type mice, in contrast to CFA. This underscored the substantial impact of the adjuvant on self‐antigen tolerance. Furthermore, we proposed an enhanced method for establishing a PV model through adoptive transfer, substituting CFA with TLR ligands. Our results revealed that in contrast to the perception that CFA being the most potent immunopotentiator reported, CFA promoted regulatory T cells (Treg), follicular regulatory T cells and IL‐10‐producing neutrophils, whereas TLR ligands downregulated CCL17 and IL‐10. This suggested potential implications for the recruitment and activation of Treg subsets. While B cell and CD8+ T cell responses exhibited similarity, CFA induced less activation in dendritic cell subsets. A novel mouse model of PV and systemic comparison of immunostimulatory effects of adjuvants were provided by this study.ConclusionsThe systematic comparison of CFA and TLR ligands shed light on the distinctive properties of these adjuvants, presenting innovative mouse models for the investigation of pemphigus. This study significantly contributes to adjuvant research and advances our understanding of PV pathogenesis.Key points/highlights Immunization with desmoglein 3 and Toll‐like receptor (TLR) ligands effectively induces pemphigus symptoms in wild‐type mice, whereas complete Freund's adjuvant (CFA) fails. TLR ligands heightened the autoreactivity of donor cells in the adoptive transfer pemphigus model. CFA promoted regulatory T cells and IL‐10‐producing neutrophils, whereas TLR ligands downregulated CCL17 and IL‐10, leading to more effective immune responses.

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Integrative single-cell analysis reveals distinct adaptive immune signatures in the cutaneous lesions of pemphigus

Xu,

Zhang,

Wang

et al. 2024

Journal of Autoimmunity

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Desmoglein-Specific B-Cell−Targeted Single-Cell Analysis Revealing Unique Gene Regulation in Patients with Pemphigus

Cited by 6 publications

References 52 publications

From neglect to spotlight: the underappreciated role of B cells in cutaneous inflammatory diseases

From neglect to spotlight: the underappreciated role of B cells in cutaneous inflammatory diseases

Immunostimulatory effects of Toll‐like receptor ligands as adjuvants in establishing a novel mouse model for pemphigus vulgaris

Integrative single-cell analysis reveals distinct adaptive immune signatures in the cutaneous lesions of pemphigus

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