A Niche for Plasma Cells: The Skin

Karaaslan, Selda; Tomayko, Mary M.

doi:10.1016/j.jid.2019.06.133

Cited by 5 publications

(5 citation statements)

References 11 publications

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“…After activation of naïve B cells, plasma cells are generated and persistently produce antibodies while receiving survival signals, mediated by the BAFF axis and IL-6, originating from adjacent cells [ 81 ]. Plasma cells can reside and accumulate at the site of inflammation [ 91 ]. Even in the absence of antigens, plasma cells can produce antibodies, as they receive survival signals via BAFF or IL-6 [ 18 ].…”

Section: Pathogenesismentioning

confidence: 99%

Cutaneous Lupus Erythematosus: An Update on Pathogenesis and Future Therapeutic Directions

et al. 2023

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Lupus erythematosus comprises a spectrum of autoimmune diseases that may affect various organs (systemic lupus erythematosus [SLE]) or the skin only (cutaneous lupus erythematosus [CLE]). Typical combinations of clinical, histological and serological findings define clinical subtypes of CLE, yet there is high interindividual variation. Skin lesions arise in the course of triggers such as ultraviolet (UV) light exposure, smoking or drugs; keratinocytes, cytotoxic T cells and plasmacytoid dendritic cells (pDCs) establish a self-perpetuating interplay between the innate and adaptive immune system that is pivotal for the pathogenesis of CLE. Therefore, treatment relies on avoidance of triggers and UV protection, topical therapies (glucocorticosteroids, calcineurin inhibitors) and rather unspecific immunosuppressive or immunomodulatory drugs. Yet, the advent of licensed targeted therapies for SLE might also open new perspectives in the management of CLE. The heterogeneity of CLE might be attributable to individual variables and we speculate that the prevailing inflammatory signature defined by either T cells, B cells, pDCs, a strong lesional type I interferon (IFN) response, or combinations of the above might be suitable to predict therapeutic response to targeted treatment. Therefore, pretherapeutic histological assessment of the inflammatory infiltrate could stratify patients with refractory CLE for T-cell-directed therapies (e.g. dapirolizumab pegol), B-cell-directed therapies (e.g. belimumab), pDC-directed therapies (e.g. litifilimab) or IFN-directed therapies (e.g. anifrolumab). Moreover, Janus kinase (JAK) and spleen tyrosine kinase (SYK) inhibitors might broaden the therapeutic armamentarium in the near future. A close interdisciplinary exchange with rheumatologists and nephrologists is mandatory for optimal treatment of lupus patients to define the best therapeutic strategy.

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Section: Pathogenesismentioning

confidence: 99%

Cutaneous Lupus Erythematosus: An Update on Pathogenesis and Future Therapeutic Directions

et al. 2023

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“…Apart from that, a few studies indicate a localized secretion of antibodies at the site of inflammation and even in healthy human skin, in which PCs secreting IgA antibodies were found to reside at eccrine sweat glands [62][63][64]. Skin-residing PCs may develop independently of T cells and accumulate in inflamed skin [65,66]. They are dependent on survival and proliferation-stimulating factors such as BLyS and APRIL, which have been shown to be upregulated in inflammatory skin [67,68].…”

Section: Plasma Cells (Pcs)mentioning

confidence: 99%

Skin-Associated B Cells in the Pathogenesis of Cutaneous Autoimmune Diseases—Implications for Therapeutic Approaches

Fetter

Niebel

Braegelmann

et al. 2020

Cells

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B lymphocytes are crucial mediators of systemic immune responses and are known to be substantial in the pathogenesis of autoimmune diseases with cutaneous manifestations. Amongst them are lupus erythematosus, dermatomyositis, systemic sclerosis and psoriasis, and particularly those driven by autoantibodies such as pemphigus and pemphigoid. However, the concept of autoreactive skin-associated B cells, which may reside in the skin and locally contribute to chronic inflammation, is gradually evolving. These cells are believed to differ from B cells of primary and secondary lymphoid organs and may provide additional features besides autoantibody production, including cytokine expression and crosstalk to autoreactive T cells in an antigen-presenting manner. In chronically inflamed skin, B cells may appear in tertiary lymphoid structures. Those abnormal lymph node-like structures comprise a network of immune and stromal cells possibly enriched by vascular structures and thus constitute an ideal niche for local autoimmune responses. In this review, we describe current considerations of different B cell subsets and their assumed role in skin autoimmunity. Moreover, we discuss traditional and B cell-associated approaches for the treatment of autoimmune skin diseases, including drugs targeting B cells (e.g., CD19- and CD20-antibodies), plasma cells (e.g., proteasome inhibitors, CXCR4 antagonists), activated pathways (such as BTK- and PI3K-inhibitors) and associated activator molecules (BLyS, APRIL).

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“…HEVs are specialized post‐capillary venules expressing a set of genes such as peripheral and mucosal addressins (PNAd), that allow naïve and central memory cells to enter the tissue where B cells can interact with their cognate antigen 23 . All these elements promote local B cell responses within the tissue and support ectopic GC formation, Ig synthesis, isotype switching and somatic hypermutation 24,25 . Alternatively, the skin can attract ASCs from the periphery, leading to their massive accumulation at inflamed sites 26 .…”

Section: Introductionmentioning

confidence: 99%

“…23 All these elements promote local B cell responses within the tissue and support ectopic GC formation, Ig synthesis, isotype switching and somatic hypermutation. 24,25 Alternatively, the skin can attract ASCs from the periphery, leading to their massive accumulation at inflamed sites. 26 Consistent with these findings, we hypothesized that BP skin harbours ASCs that contribute to Ig secretion and enhance the local concentration of antibodies.…”

Section: Introductionmentioning

confidence: 99%

Presence of immunoglobulin E‐expressing antibody‐secreting cells in the dermis close to bullous pemphigoid lesions

Budair,

Kambe,

Kogame

et al. 2024

Experimental Dermatology

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Antibody‐secreting cells (ASCs) produce immunoglobulin (Ig) G and IgE autoantibodies in secondary lymphoid organs. Evidence also suggests their existence in the skin in various chronic inflammatory conditions, and in association with CXCL12 and CXCL13, they regulate the recruitment/survival of ASCs and germinal center formation to generate ASCs, respectively. However, the presence of IgG and IgE in bullous pemphigoid (BP) lesions needs to be addressed. Here, we aimed to analyse BP skin for the presence of IgG and IgE and the factors contributing to their generation, recruitment, and persistence. Skin samples from 30 patients with BP were stained to identify ASCs and the immunoglobulin type they expressed. The presence of tertiary lymphoid organ (TLO) elements, which generate ASCs in non‐lymphoid tissues, and the chemokines CXCL12 and CXCL13, which regulate the migration/persistence of ASCs in lymphoid tissues and formation of TLOs, respectively, were evaluated in BP skin. BP skin harboured ASCs expressing the two types of antibodies IgG and IgE. ASCs were found in high‐grade cellular aggregates containing TLO elements: T cells, B cells, CXCL12+ cells, CXCL13+ cells and high endothelial venules. IgG+ ASCs were detected among these aggregates, whereas IgE+ ASCs were dispersed throughout the dermis. CXCL12+ fibroblast‐like cells were located close to ASCs. The inflammatory microenvironment of BP lesions may contribute to the antibody load characteristic of the skin of patients with BP by providing a site for the presence of ASCs. CXCL13 and CXCL12 expression may contribute to the generation and recruitment/survival of ASCs, respectively.

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A Niche for Plasma Cells: The Skin

Abstract: Farhi A, et al. Mitotic recombination in patients with ichthyosis causes reversion of dominant mutations in KRT10. Science 2010;330:94e7.

Cited by 5 publications

References 11 publications

Cutaneous Lupus Erythematosus: An Update on Pathogenesis and Future Therapeutic Directions

Cutaneous Lupus Erythematosus: An Update on Pathogenesis and Future Therapeutic Directions

Skin-Associated B Cells in the Pathogenesis of Cutaneous Autoimmune Diseases—Implications for Therapeutic Approaches

Presence of immunoglobulin E‐expressing antibody‐secreting cells in the dermis close to bullous pemphigoid lesions

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