Bullous pemphigoid outcome is associated with CXCL10-induced matrix metalloproteinase 9 secretion from monocytes and neutrophils but not lymphocytes

Riani, Meriem; Jan, Sébastien Le; Plée, Julie; Durlach, A.; Naour, Richard Le; Haegeman, Guy; Bernard, Philippe; Antonicelli, Frank

doi:10.1016/j.jaci.2016.08.012

Cited by 57 publications

(71 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In this study, numerous functional antimicrobial proteins and enzymes, such as lactoferrin, OLFM4, LCN2, S100A8, and MMP9, were found in neutrophil exosomes, highlighting their importance in different molecular functions such as defense against bacteria and phagosomes and regulation of inflammatory genes. For instance, MMP9 plays an important role in neutrophil migration across the endothelial barrier into tissues, which has implications in bullous pemphigoid or other skin diseases (39,63,64). Also, MMP9 can be secreted to form a complex with LCN2, and this MMP9-neutrophil gelatinase-associated lipocalin complex has been associated with cancer metastasis and inflammation (65,66).…”

Section: Discussionmentioning

confidence: 99%

“…As the results showed, OLFM4 was mainly expressed and located in neutrophils in pustules, but not in dermis. MMP9, a key molecule involved in the inflammatory infiltration and proteolytic cascade (39), was intensively expressed by neutrophils in skin lesions of GPP but not observed in normal skin. LCN2, S100A8, and S100A8/A9 heterodimer are vital AMPs that regulate neutrophil chemotaxis and secretion (30,36) and were shown to be rich in the epidermis and infiltrated neutrophils in GPP skin lesions (Fig.…”

Section: Proteome Profiling Shows Abundance Of Inflammatory Proteins mentioning

confidence: 91%

See 1 more Smart Citation

Neutrophil exosomes enhance the skin autoinflammation in generalized pustular psoriasis via activating keratinocytes

et al. 2019

View full text Add to dashboard Cite

Generalized pustular psoriasis (GPP) is a rare and severe inflammatory skin disease that can be life‐threatening. Gene mutations are found in some cases, but its immune pathogenesis is largely unknown. Here, we observed that the neutrophil:lymphocyte ratio in patients with GPP was higher than that in healthy controls and decreased after effective treatment. Neutrophils isolated from patients with GPP induced higher expressions of inflammatory genes including IL‐1β, IL‐36G, IL‐18, TNF‐α, and C‐X‐C motif chemokine ligands in keratinocytes than normal neutrophils did. Moreover, neutrophils from patients with GPP secreted more exosomes than controls, which were then rapidly internalized by keratinocytes, increasing the expression of these inflammatory molecules via activating NF‐κB and MAPK signaling pathways. The proteomic profiles in neutrophil exosomes further characterized functional proteins and identified olfactomedin 4 as the critical differentially expressed protein that mediates the autoimmune inflammatory responses of GPP. These results demonstrate that neutrophil exosomes have an immune‐regulatory effect on keratinocytes, which modulates immune cell migration and autoinflammation in GPP.—Shao, S., Fang, H., Zhang, J., Jiang, M., Xue, K., Ma, J., Zhang, J., Lei, J., Zhang, Y., Li, B., Yuan, X., Dang, E., Wang, G. Neutrophil exosomes enhance the skin autoinflammation in generalized pustular psoriasis via activating keratinocytes. FASEB J. 33, 6813–6828 (2019). http://www.fasebj.org

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Proteome Profiling Shows Abundance Of Inflammatory Proteins mentioning

confidence: 91%

Neutrophil exosomes enhance the skin autoinflammation in generalized pustular psoriasis via activating keratinocytes

et al. 2019

View full text Add to dashboard Cite

show abstract

“…To understand the mechanisms for the induction of MMPs in skin, IL-17-related inflammatory models are important. Indeed, the significance of IL-17 was reported in autoimmune diseases such as psoriasis [15], bullous pemphigoid (BP) [16,17], and alopecia areata [18]. Among them, Riani et al [16] reported that IL-17 increased CXCL10 in inflammatory cells, leading to an augmented secretion of MMP9 from neutrophils and monocytes in BP patients.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, the significance of IL-17 was reported in autoimmune diseases such as psoriasis [15], bullous pemphigoid (BP) [16,17], and alopecia areata [18]. Among them, Riani et al [16] reported that IL-17 increased CXCL10 in inflammatory cells, leading to an augmented secretion of MMP9 from neutrophils and monocytes in BP patients. Notably, MMP9 remodels the extracellular matrix and promotes the sprouting and growth of new blood vessels [19] and, as we have previously reported, most cutaneous angiosarcomas produce MMP9 [20].…”

Section: Discussionmentioning

confidence: 99%

IL-23 Expression in Stewart-Treves Syndrome: Two Case Reports and Immunohistochemical Investigation

et al. 2020

View full text Add to dashboard Cite

Stewart-Treves syndrome (STS) is a rare cutaneous lymphangiosarcoma developing from chronic lymph edema as a consequence of radical mastectomy or surgical invasion of the groin for the treatment of cervical or penile cancer. Previous reports suggested possible mechanisms in the development of lymphangiosarcoma that correlate with the immunological background of STS patients. In this report, we described two cases of STS developing in patients who underwent radical dissection for cervical cancer, we employed immunohistochemical staining of IL-23 and IL-17. Case ReportCase 1 A 79-year-old Japanese woman visited our outpatient clinic with a 1-month history of a red, easy to bleed, nodule on the right femur. She had undergone resection of a cervical cancer 24 years before and developed prominent lymph edema in the lower extremities. During her initial visit, physical examination revealed a dark-red nodule with extended purpura on the right femur together with prominent lymph edema (Fig. 1a). Histologically, these were irregularly anastomosing vascular channels lined by single layers of enlarged, atypical endothelial cells that existed between the collagen bundles (Fig. 1b). Immunohistochemical staining revealed that these atypical endothelial cells were positive for vimentin, CD31, CD34, D2-40, and Factor VIII. The Ki67 score was 90%. Moreover, a substantial number of IL-23-producing cells (Fig. 1c) as well as IL-17-producing cells (Fig. 1d) were detected at the edge of the tumor mass. Positron emission tomography scans showed no evidence of metastases. From the

show abstract

“…Studies showing that antibodies targeting areas outside of NC16A had less capacity to deplete COL17 on keratinocytes than antibodies targeting NC16A suggest that the pathogenicity of autoantibodies in BP could be epitope dependent 61, 62 . Recent studies have offered some biomarkers for more efficient diagnosis and prediction of prognosis in pemphigoid 63, 64 .…”

Section: Pemphigoidmentioning

confidence: 99%

Recent advances in the understanding and treatment of pemphigus and pemphigoid

Yamagami¹

2018

F1000Res

View full text Add to dashboard Cite

Pemphigus and pemphigoid are characterized as autoimmune blistering diseases in which immunoglobulin G autoantibodies cause blisters and erosions of the skin or mucosa or both. Recently, understanding of the pathophysiology of pemphigus and pemphigoid has been furthered by genetic analyses, characterization of autoantibodies and autoreactive B cells, and elucidation of cell–cell adhesion between keratinocytes. For the management of pemphigus and pemphigoid, the administration of systemic corticosteroids still represents the standard treatment strategy; however, evidence of the efficacy of therapies not involving corticosteroids, such as those employing anti-CD20 antibodies, is increasing. The goal should be to develop antigen-specific immune suppression-based treatments.

show abstract

Bullous pemphigoid outcome is associated with CXCL10-induced matrix metalloproteinase 9 secretion from monocytes and neutrophils but not lymphocytes

Abstract: We showed that increased levels of inflammatory biomarkers in patients with BP, such as CXCL10, favor neutrophil- and monocyte-associated MMP-9 release and disease relapse and opened new therapeutic horizons in patients with this autoimmune disease.

Cited by 57 publications

References 43 publications

Neutrophil exosomes enhance the skin autoinflammation in generalized pustular psoriasis via activating keratinocytes

Neutrophil exosomes enhance the skin autoinflammation in generalized pustular psoriasis via activating keratinocytes

IL-23 Expression in Stewart-Treves Syndrome: Two Case Reports and Immunohistochemical Investigation

Recent advances in the understanding and treatment of pemphigus and pemphigoid

Contact Info

Product

Resources

About