Type I interferon in the pathogenesis of systemic lupus erythematosus

Current Opinion in Immunology, Journal Year: 2020, Volume and Issue: 67, P. 87 - 94

Published: Nov. 24, 2020

Language: Английский

---

Unmet Medical Needs in Chronic, Non-communicable Inflammatory Skin Diseases

Frontiers in Medicine, Journal Year: 2022, Volume and Issue: 9

Published: June 9, 2022

An estimated 20-25% of the population is affected by chronic, non-communicable inflammatory skin diseases. Chronic inflammation has many causes. Among most frequent chronic diseases are atopic dermatitis, psoriasis, urticaria, lichen planus, and hidradenitis suppurativa, driven a complex interplay genetics environmental factors. Autoimmunity another important cause inflammation. The autoimmune response may be mainly T cell driven, such as in alopecia areata or vitiligo, B spontaneous pemphigus pemphigoid Rare causes autoinflammatory diseases, rheumatic cutaneous lupus erythematosus dermatomyositis. Whilst we have seen significant improvement diagnosis treatment, several challenges remain. Especially for rarer inflammation, early often missed because low awareness lack diagnostics. Systemic immunosuppression treatment choice almost all these Adverse events due to immunosuppression, insufficient therapeutic responses relapses remain challenge. For dermatitis broad spectrum innovative treatments been developed. However, cannot predicted so far. Hence, development (bio)markers allowing selection specific medications individual patients needed. Given encouraging developments during past years, envision that will thoroughly addressed future.

Language: Английский

---

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

American Journal of Clinical Dermatology, Journal Year: 2023, Volume and Issue: 24(4), P. 521 - 540

Published: May 4, 2023

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

Language: Английский

---

Understanding genomics and the immune environment of penile cancer to improve therapy

Nature Reviews Urology, Journal Year: 2020, Volume and Issue: 17(10), P. 555 - 570

Published: Aug. 18, 2020

Language: Английский

---

AIM2 and Psoriasis

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Jan. 18, 2023

Psoriasis is a chronic inflammatory skin disease occurring worldwide, with multiple systemic complications, which seriously affect the quality of life and physical mental health patients. The pathogenesis psoriasis related to environment, genetics, epigenetics, dysregulation immune cells such as T cells, dendritic (DCs), nonimmune keratinocytes. Absent in melanoma 2 (AIM2), susceptibility gene locus for psoriasis, has been strongly linked genetic epigenetic aspects increased expression psoriatic AIM2 was found be activated an inflammasome-dependent way release IL-1β IL-18 mediate inflammation, participate regulation or inflammasome-independent by regulating function regulatory T(Treg) programming cell death keratinocytes well controlling proliferative state different cells. may also play role recurrence trained immunity. In this review, we will elaborate on characteristics how mediates development psoriasis.

Language: Английский

---

SOCS-JAK-STAT inhibitors and SOCS mimetics as treatment options for autoimmune uveitis, psoriasis, lupus, and autoimmune encephalitis

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 26, 2023

Autoimmune diseases arise from atypical immune responses that attack self-tissue epitopes, and their development is intricately connected to the disruption of JAK-STAT signaling pathway, where SOCS proteins play crucial roles. Conditions such as autoimmune uveitis, psoriasis, lupus, encephalitis exhibit system dysfunctions associated with dysregulation. Emerging therapeutic strategies utilize inhibitors mimetics modulate alleviate manifestations. Although more research clinical studies are required assess effectiveness, safety profiles, potential for personalized approaches in conditions, show promise treatment options. This review explores action, future prospects JAK agents systemic lupus erythematosus, encephalitis. The findings underscore importance investigating these targeted therapies advance options individuals suffering diseases.

Language: Английский

---

Baricitinib Attenuates Autoimmune Phenotype and Podocyte Injury in a Murine Model of Systemic Lupus Erythematosus

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Aug. 23, 2021

Baricitinib, a selective inhibitor for janus kinase (JAK) 1 and JAK2, is approved use in rheumatoid arthritis. Systemic lupus erythematosus (SLE) recently regarded as potential candidate targeted by JAK inhibitors because of the relationship between its pathogenesis JAK/signal transducer activator transcription (STAT) pathway-mediated cytokines such type I interferons. The objective this study was to determine whether baricitinib could effectively ameliorate SLE using murine model. To investigate effects on various autoimmune features, especially renal involvements SLE, eight-week-old MRL/Mp-Faslpr (MRL/lpr) mice were used lupus-prone animal model treated with eight weeks. Immortalized podocytes primary B cells isolated from C57BL/6 vitro efficacy baricitinib. Baricitinib remarkably suppressed lupus-like phenotypes MRL/lpr mice, splenomegaly, lymphadenopathy, proteinuria, systemic autoimmunity including circulating autoantibodies pro-inflammatory cytokines. It also modulated immune cell populations ameliorated inflammation, leading recovery expression structural proteins podocytes. According experiments, treatment mitigate differentiation restore disrupted cytoskeletal structures under inflammatory stimulation blocking JAK/STAT pathway. present demonstrated that attenuate features inflammation suppressing aberrant activation podocyte abnormalities. Thus, be promising therapeutic SLE.

Language: Английский

---

Current Status of Baricitinib as a Repurposed Therapy for COVID-19

Pharmaceuticals, Journal Year: 2021, Volume and Issue: 14(7), P. 680 - 680

Published: July 15, 2021

The emergence of the COVID-19 pandemic has mandated instant (re)search for potential drug candidates. In response to unprecedented situation, it was recognized early that repurposing available drugs in market could timely save lives, by skipping lengthy phases preclinical and initial safety studies. BenevolentAI’s large knowledge graph repository structured medical information suggested baricitinib, a Janus-associated kinase inhibitor, as repurposed medicine with dual mechanism; hindering SARS-CoV2 entry combatting cytokine storm; leading cause mortality COVID-19. However, recently-published Adaptive Treatment Trial-2 (ACTT-2) positioned baricitinib only combination remdesivir treatment specific category patients, whereas is not recommended be used alone except clinical trials. increased pace data output all life sciences fields changed our understanding processing manipulation. For purpose design, development, or repurposing, integration different disciplines highly achieve ultimate benefit using new technologies mine BIG data, however, final say remains concluded after practice. This review demonstrates bioinformatics, chemical, pharmacological, aspects highlight journey evaluates its placement current guidelines treatment.

Language: Английский

---

Current Concepts on Pathogenic Mechanisms and Histopathology in Cutaneous Lupus Erythematosus

Frontiers in Medicine, Journal Year: 2022, Volume and Issue: 9

Published: May 30, 2022

Cutaneous lupus erythematosus (CLE) is an interferon (IFN)-driven autoimmune disease that may be limited to the skin or can associated with systemic (SLE). CLE occurs in several morphologic subtypes ranging from isolated, disc-shaped plaques disseminated lesions. The typical histopathologic pattern of lesions named interface dermatitis and characterized by a lymphocytic infiltrate necroptotic keratinocytes at dermo-epidermal junction. Other patterns primarily involve dermis subcutis, depending on subtype. One critical mechanism chronic reactivation innate adaptive immune pathways. An important step this process recognition endogenous nucleic acids released dying cells various receptors (PRRs), including Toll-like (TLRs) other cytosolic receptors. Crucial pathogenesis comprise plasmacytoid dendritic (pDCs) as major producers type I IFN, T exerting cytotoxic effects, B cells, previously believed contribute via secretion autoantibodies. However, are increasingly considered have additional functions, supported studies finding them occur highest numbers discoid (CDLE), subtype which autoantibodies often absent. More precise knowledge how differ pathophysiologically allow tailored pharmacotherapy future, taking into account specific molecular signature relation

Language: Английский

---

Why Do We Need JAK Inhibitors in Systemic Lupus Erythematosus?

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(19), P. 11788 - 11788

Published: Oct. 4, 2022

Systemic lupus erythematosus (SLE) is a chronic, multifactorial autoimmune disease with complex pathogenesis characterized by the imbalance of pro-inflammatory and anti-inflammatory cytokines. Janus kinases (JAKs), intracellular non-receptor tyrosine kinases, are essential for signal pathways many The JAK transducers activators transcription (STAT) consist four seven STATs family members. dysregulation JAK-STAT represents an important process in SLE. Thus, use therapies that target specific signaling would be challenge It well known inhibitors have real potential treatment rheumatic diseases, but their efficacy SLE remains to determined. currently being investigated phase II III trials considered become next stage therapy. In this review, we report current data regarding development clinically useful kinase might improve upon traditional therapeutic strategies.

Language: Английский

---