scholarly journals Multifaceted contribution of the TLR4-activated IRF5 transcription factor in systemic sclerosis

2015 ◽  
Vol 112 (49) ◽  
pp. 15136-15141 ◽  
Author(s):  
Ryosuke Saigusa ◽  
Yoshihide Asano ◽  
Takashi Taniguchi ◽  
Takashi Yamashita ◽  
Yohei Ichimura ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Cell Activation ◽  
Susceptibility Gene ◽  
Clinical Manifestations ◽  
Autoimmune Disorder ◽  
Skin Lesions ◽  
B Cell Activation ◽  
Mesenchymal Transition ◽  
Endothelial To Mesenchymal Transition ◽  
High Level

Systemic sclerosis (SSc) is a multisystem autoimmune disorder with clinical manifestations resulting from tissue fibrosis and extensive vasculopathy. A potential disease susceptibility gene for SSc is IFN regulatory factor 5 (IRF5), whose SNP is associated with milder clinical manifestations; however, the underlying mechanisms of this association remain elusive. In this study we examined IRF5-deficient (Irf5−/−) mice in the bleomycin-treated SSc murine model. We show that dermal and pulmonary fibrosis induced by bleomycin is attenuated in Irf5−/− mice. Interestingly, we find that multiple SSc-associated events, such as fibroblast activation, inflammatory cell infiltration, endothelial-to-mesenchymal transition, vascular destabilization, Th2/Th17 skewed immune polarization, and B-cell activation, are suppressed in these mice. We further provide evidence that IRF5, activated by Toll-like receptor 4 (TLR4), binds to the promoters of various key genes involved in SSc disease pathology. These observations are congruent with the high level of expression of IRF5, TLR4, and potential endogenous TLR4 ligands in SSc skin lesions. Our study sheds light on the TLR4-IRF5 pathway in the pathology of SSc with clinical implications of targeting the IRF5 pathways in the suppression of disease development.

Involvement of scalp and nails in lupus erythematosus

Lupus ◽  
2010 ◽  
Vol 19 (9) ◽  
pp. 1078-1086 ◽  
Author(s):  
RM Trüeb
Keyword(s):  
Disease Activity ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Cutaneous Lupus Erythematosus ◽  
Autoimmune Disorder ◽  
Skin Lesions ◽  
B Cell Activation ◽  
Autoantibody Production ◽  
Life Threatening ◽  
The Many

Lupus erythematosus (LE) is a systemic autoimmune disorder associated with polyclonal B-cell activation resulting in diverse patterns of autoantibody production and a heterogeneous clinical expression constituting a spectrum extending from limited cutaneous disease to life-threatening systemic manifestations. For daily clinical practice, the characteristics of cutaneous lupus erythematosus (CLE) have been well defined in terms of morphology, and clinical and laboratory criteria are available for the classification as systemic lupus erythematosus (SLE). The many different types of skin lesions encountered in patients with LE have been classified into those that are histologically specific for LE and those that are not. While LE non-specific skin lesions on their own do not enable a diagnosis of LE, they can be important reflections of underlying SLE disease activity. This also applies to the involvement of the scalp and nails. Finally, it must be kept in mind that LE patients may also develop drug-related, or other unrelated common disorders of the hair and nails that do not reflect LE disease activity. Lupus (2010) 19, 1078—1086.

scholarly journals A Potential Link Between Oxidative Stress and Endothelial-to-Mesenchymal Transition in Systemic Sclerosis

2018 ◽  
Vol 9 ◽  
Author(s):  
Duong Thi Bich Thuan ◽  
Hatem Zayed ◽  
Ali H. Eid ◽  
Haissam Abou-Saleh ◽  
Gheyath K. Nasrallah ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Systemic Sclerosis ◽  
Mesenchymal Transition ◽  
Potential Link ◽  
Endothelial To Mesenchymal Transition

scholarly journals Macrophages Guard Endothelial Lineage by Hindering Endothelial-to-Mesenchymal Transition: Implications for the Pathogenesis of Systemic Sclerosis

2019 ◽  
Vol 203 (1) ◽  
pp. 247-258 ◽  
Author(s):  
Pier Andrea Nicolosi ◽  
Enrico Tombetti ◽  
Anna Giovenzana ◽  
Eleonora Donè ◽  
Eleonora Pulcinelli ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Mesenchymal Transition ◽  
Endothelial Lineage ◽  
Endothelial To Mesenchymal Transition

scholarly journals Bosentan and macitentan prevent the endothelial-to-mesenchymal transition (EndoMT) in systemic sclerosis: in vitro study

2016 ◽  
Vol 18 (1) ◽  
Author(s):  
Claudio Corallo ◽  
Maurizio Cutolo ◽  
Bashar Kahaleh ◽  
Gianluca Pecetti ◽  
Antonio Montella ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
In Vitro Study ◽  
Vitro Study ◽  
Mesenchymal Transition ◽  
Endothelial To Mesenchymal Transition

scholarly journals A new paradigm for leprosy diagnosis based on host gene expression

2021 ◽  
Author(s):  
Thyago Leal-Calvo ◽  
Charlotte Avanzi ◽  
Mayara A Mendes ◽  
Andrej Benjak ◽  
Philippe Busso ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Transcriptional Profiling ◽  
Clinical Manifestations ◽  
Skin Lesions ◽  
Therapeutic Interventions ◽  
Diagnostic Tools ◽  
New Paradigm ◽  
Mesenchymal Transition ◽  
Ido1 Expression ◽  
Leprosy Patients

Transcriptional profiling is a powerful tool to investigate and detect human diseases. In this study, we used bulk RNA-sequencing (RNA-Seq) to compare the transcriptomes in skin lesions of leprosy patients or matched controls affected by other dermal conditions such as granuloma annulare, a confounder for paucibacillary leprosy. We identified five genes capable of accurately distinguishing multibacillary and paucibacillary leprosy from other skin conditions. Indoleamine 2,3-dioxygenase 1 ( IDO1 ) expression alone was highly discriminatory, followed by TLR10, BLK, CD38, and SLAMF7, whereas the HS3ST2 and CD40LG mRNA separated multi- and paucibacillary leprosy. Finally, from the main differentially expressed genes (DEG) and enriched pathways, we conclude that paucibacillary disease is characterized by epithelioid transformation and granuloma formation, with an exacerbated cellular immune response, while multibacillary leprosy features epithelial-mesenchymal transition with phagocytic and lipid biogenesis patterns in the skin. These findings will help catalyze the development of better diagnostic tools and potential host-based therapeutic interventions. Finally, our data may help elucidate host-pathogen interplay driving disease clinical manifestations.

scholarly journals Essential syphilitic alopecia: Non-scarring alopecia in 21-year-old man

2021 ◽  
Vol 12 (e) ◽  
pp. 1-3
Author(s):  
Hafssa Chehab ◽  
Bertrand Richert
Keyword(s):  
Hair Loss ◽  
Previous History ◽  
Treponema Pallidum ◽  
Clinical Manifestations ◽  
Skin Lesions ◽  
Secondary Syphilis ◽  
Laboratory Evaluation ◽  
History Of ◽  
High Level

ABSTRACT Alopecia syphilitica is a less common clinical manifestations of secondary syphilis. It is uncommon for hair loss to be the sole or predominant manifestation, as hair loss is the chief clinical and histologic differential diagnosis of. The main difference between alopecia areata and Alopecia syphilitica is the detection of Treponema pallidum in syphilis. We present the case of a 21- year-old belgium man with different patches of non-cicatricial alopecia of his scalp. The patient denied previous history of genital or other skin lesions. Laboratory evaluation was positive for syphilis. The diagnosis of alopecia syphilitica was made and he was treated with single intramuscular injections of benzathine penicillin. The lesions improved with treatment in all the patients who attended follow-up. Dermatologists should maintain a high level of clinical suspicion for this uncommon manifestation of syphilis, particularly when it is the only symptom.

scholarly journals The Role of Fibrinolytic Regulators in Vascular Dysfunction of Systemic Sclerosis

2019 ◽  
Vol 20 (3) ◽  
pp. 619 ◽  
Author(s):  
Yosuke Kanno
Keyword(s):  
Systemic Sclerosis ◽  
Plasminogen Activator ◽  
Vascular Dysfunction ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Type ◽  
Plasminogen Activator Inhibitor 1 ◽  
Mesenchymal Transition ◽  
Type Plasminogen Activator ◽  
Endothelial To Mesenchymal Transition ◽  
Endothelial Homeostasis

Systemic sclerosis (SSc) is a connective tissue disease of autoimmune origin characterized by vascular dysfunction and extensive fibrosis of the skin and visceral organs. Vascular dysfunction is caused by endothelial cell (EC) apoptosis, defective angiogenesis, defective vasculogenesis, endothelial-to-mesenchymal transition (EndoMT), and coagulation abnormalities, and exacerbates the disease. Fibrinolytic regulators, such as plasminogen (Plg), plasmin, α2-antiplasmin (α2AP), tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA) and its receptor (uPAR), plasminogen activator inhibitor 1 (PAI-1), and angiostatin, are considered to play an important role in the maintenance of endothelial homeostasis, and are associated with the endothelial dysfunction of SSc. This review considers the roles of fibrinolytic factors in vascular dysfunction of SSc.

Clinical Manifestations of Scleroderma

1995 ◽  
Vol 16 (2) ◽  
pp. 49-49
Author(s):  
Patricia L. Haber
Keyword(s):  
Systemic Sclerosis ◽  
Connective Tissue ◽  
Clinical Manifestations ◽  
Skin Lesions ◽  
Localized Scleroderma ◽  
Unknown Etiology ◽  
Collagen Deposition ◽  
Muscle Fibrosis ◽  
Favorable Prognosis ◽  
Organ Systems

Scleroderma is a connective tissue disease of unknown etiology. Its most characteristic feature is thickening of the skin due to increased collagen deposition. However, the disease may involve multiple other organ systems. Two broad categories of scleroderma have been defined: localized and systemic. Although all forms of scleroderma are rare, localized scleroderma occurs more frequently than systemic sclerosis and has a more favorable prognosis. Several types of localized scleroderma exist. Morphea is characterized by the presence of one or more patches of hard, ivory-colored skin lesions. They begin with erythema and progress to nonpitting edema before becoming sclerotic. The margins of active lesions often have a violaceous hue. Underlying muscle fibrosis and atrophy may occur.

scholarly journals Gene Expression Profiling in Behcet’s Disease Indicates an Autoimmune Component in the Pathogenesis of the Disease and Opens New Avenues for Targeted Therapy

2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
Antonio Puccetti ◽  
Piera Filomena Fiore ◽  
Andrea Pelosi ◽  
Elisa Tinazzi ◽  
Giuseppe Patuzzo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Network Analysis ◽  
Cell Activation ◽  
Skin Lesions ◽  
Specific Gene ◽  
Type I ◽  
B Cell Activation ◽  
Multisystem Disease ◽  
Healthy Donors ◽  
Activation Pathways

Behçet disease (BD) is a chronic inflammatory multisystem disease characterized by oral and genital ulcers, uveitis, and skin lesions. Disease etiopathogenesis is still unclear. We aim to elucidate some aspects of BD pathogenesis and to identify specific gene signatures in peripheral blood cells (PBCs) of patients with active disease using novel gene expression and network analysis. 179 genes were modulated in 10 PBCs of BD patients when compared to 10 healthy donors. Among differentially expressed genes the top enriched gene function was immune response, characterized by upregulation of Th17-related genes and type I interferon- (IFN-) inducible genes. Th17 polarization was confirmed by FACS analysis. The transcriptome identified gene classes (vascular damage, blood coagulation, and inflammation) involved in the pathogenesis of the typical features of BD. Following network analysis, the resulting interactome showed 5 highly connected regions (clusters) enriched in T and B cell activation pathways and 2 clusters enriched in type I IFN, JAK/STAT, and TLR signaling pathways, all implicated in autoimmune diseases. We report here the first combined analysis of the transcriptome and interactome in PBCs of BD patients in the active stage of disease. This approach generates useful insights in disease pathogenesis and suggests an autoimmune component in the origin of BD.

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