Neutrophilic granulocyte-derived B-cell activating factor supports B cells in skin lesions in hidradenitis suppurativa

Sabat, Robert; Šimaitė, Deimantė; Guðjónsson, Jóhann E.; Brembach, Theresa-Charlotte; Witte, Katrin; Krause, Torben; Kokolakis, Georgios; Bartnik, Eckart; Nikolaou, Christos; Rill, Natascha; Coulibaly, Bema; Levin, Clément; Herrmann, Matthias; Salinas, Gabriela; Leeuw, Thomas; Volk, Hans‐Dieter; Ghoreschi, Kamran; Wolk, Kerstin

doi:10.1016/j.jaci.2022.10.034

Cited by 18 publications

(30 citation statements)

References 43 publications

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“…Naive B cells are rare in healthy skin and therefore likely recruited to progressing HS lesions through the induction of a supportive tissue microenvironment complete with associated chemokines and maintenance factors 46 . In agreement with this model, we and others have previously observed significant upregulation of the B cell survival factors BAFF and APRIL in HS lesions 4,5 . That organized TLS are also induced by the HS inflammatory milieu provides further evidence for generation of a niche supportive of B cells during the progressive evolution of HS lesions.…”

supporting

confidence: 92%

“…Immune dysregulation surrounding the hair follicle following follicular occlusion is hypothesized to initiate the aberrant inflammatory process characteristic of HS plaques; however, exact disease etiology is unclear [1][2][3] . For example, immune infiltrates within HS lesions include overrepresentation of cell subsets that are rarely observed in healthy skin and other inflammatory skin diseases, especially B cells and plasma cells [4][5][6] . In addition, antibodies recognizing a broad array of autoantigens have been identified in patient sera as well as lesional skin suggesting contribution of B lineage cells to disease pathogenesis [6][7][8][9][10] .…”

Section: Discussionmentioning

confidence: 99%

“…Limited studies involving B cell depletion with rituximab hint that modulation of these cells may have therapeutic benefit 11,12 . Lymphoid aggregates comprising B cells and T cells have been described in HS lesions and are a recognized histological feature of this disease but it is unknown if organized tertiary lymphoid structures (TLS) capable of sustaining cutaneous B cell activity in situ are present 1,4,13 . To understand the dynamics and microenvironmental interactions of B cells within HS lesions, we employed histological analysis, scRNAseq, and spatial transcriptomics.…”

Section: Discussionmentioning

confidence: 99%

“…As such, these structures are capable of regulating B cell immune responses by facilitating T cell help and supporting formation of germinal center reactions 14 . Lymphoid aggregates are recognized as a histological feature of HS lesions and the presence of fully formed TLS has been hypothesized; however, definitive evidence of fully functional TLS has not previously been reported 1,4,13 . Our data demonstrate that these structures are relatively common in advanced HS lesions.…”

mentioning

confidence: 99%

“…Discussion While B cell signatures are strongly evident in HS, the contribution of these lymphocytes to disease pathogenesis is unclear. Memory B cells and antibody secreting plasma cells accumulate in HS lesional skin to become a prominent immunological feature 1,[4][5][6] . Antibodies against a wide array of self-antigens are detectable in both patient sera and the skin lesions themselves suggesting ongoing B cell activity and possible contribution to disease progression [6][7][8][9] .…”

mentioning

confidence: 99%

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Tertiary Lymphoid Structures Sustain Cutaneous B cell Activity in Hidradenitis Suppurativa

Lowe

Cohen

Moss

et al. 2023

Preprint

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Hidradenitis suppurativa (HS) skin lesions are highly inflammatory and characterized by a large immune infiltrate. While B cells and plasma cells comprise a major component of this immune milieu the biology and contribution of these cells in HS pathogenesis is unclear. Here, we aimed to investigate the dynamics and microenvironmental interactions of B cells within cutaneous HS lesions. We combined histological analysis, single-cell RNA-sequencing (scRNAseq), and spatial transcriptomic profiling of HS lesions to define the tissue microenvironment relative to B cell activity within this disease. Our findings identify tertiary lymphoid structures (TLS) within HS lesions and describe organized interactions between T cells, B cells, antigen presenting cells and skin stroma. We find evidence that B cells within HS TLS actively undergo maturation, including participation in germinal center reactions and class switch recombination. Moreover, skin stroma and accumulating T cells are primed to support the formation of TLS and facilitate B cell recruitment during HS. Our data definitively demonstrate the presence of TLS in lesional HS skin and point to ongoing cutaneous B cell maturation through class switch recombination and affinity maturation during disease progression in this inflamed non-lymphoid tissue.

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supporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Tertiary Lymphoid Structures Sustain Cutaneous B cell Activity in Hidradenitis Suppurativa

Lowe

Cohen

Moss

et al. 2023

Preprint

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An Atlas of the Hidradenitis Suppurativa Transcriptome

Szukala,

Lichawska-Cieslar,

Krajewski

et al. 2024

Dermatol Ther (Heidelb)

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Introductions Hidradenitis suppurativa (HS) is a chronic inflammatory condition of the skin. Both genetic and environmental factors contribute to the risk of developing HS, but the pathogenesis of this disease is currently not fully understood. The aim of this study was to further current understanding of the molecular background of HS with the use of global transcriptome analyses. Methods Transcriptome profiling of perilesional and lesional skin of five patients with HS and six healthy control patients was performed by next-generation sequencing. Groups of differentially expressed genes characteristic of the skin of patients with HS were shortlisted by bioinformatic analysis. Results RNA sequencing followed by bioinformatic profiling revealed profound enrichment of inflammatory-related processes in both lesional and perilesional skin of patients with HS. There were, however, distinct differences in the gene expression profiles between the lesional and perilesional skin, with 1488 genes differentially expressed. Genes encoding typical proinflammatory cytokines were profoundly enriched within HS lesions. In contrast, those encoding mediators of extracellular matrix organization were highly expressed mostly in the perilesional area. Conclusions Our study provides novel insights into the mechanisms underlying the pathogenesis of HS, and the results also have potential clinical implications in both diagnosis and therapeutics.

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Hidradenitis Suppurativa Tunnels Invasive Transcriptional Signature

Caucheteux,

Piguet

2024

Journal of Investigative Dermatology

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Neutrophilic granulocyte-derived B-cell activating factor supports B cells in skin lesions in hidradenitis suppurativa

Cited by 18 publications

References 43 publications

Tertiary Lymphoid Structures Sustain Cutaneous B cell Activity in Hidradenitis Suppurativa

Tertiary Lymphoid Structures Sustain Cutaneous B cell Activity in Hidradenitis Suppurativa

An Atlas of the Hidradenitis Suppurativa Transcriptome

Hidradenitis Suppurativa Tunnels Invasive Transcriptional Signature

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