Biologics and Small-Molecule Therapies in Netherton Syndrome: A Comprehensive Review.

Netherton syndrome (NS) is a rare congenital ichthyosis caused by loss-of-function mutations in the SPINK5 gene, leading to defective expression of the serine protease inhibitor LEKTI. Dysregulated epidermal protease activity results in impaired skin barrier function and chronic inflammation, accompanied by complex immune profiles. NS patients commonly show activation of the inflammatory axis, centered on IL-17 and IL-36, in the skin and blood, and show a psoriasis-like shift to Th17.

Aberrant humoral immune responses and intestinal homeostasis in Cd38 Bst1 double knockout mice.

Bone marrow stromal cell antigen-1 (BST-1)/CD157 and CD38 are ectoenzymes belonging to the mammalian ADP-ribosyl cyclase family. Previous analyses of BST-1-deficient mice (Bst1KO) in a 129×C57BL/6J(B6) mixed background revealed that BST-1 is a positive regulator of humoral immunity. Murine BST-1 has recently been known to be an enteroneuroimmune regulator.

Consideration of useful patient-reported outcome measures to identify the unmet medical needs of children and adults with autoimmune and autoinflammatory diseases.

Patients with autoimmune and autoinflammatory diseases experience difficult physical, mental, and social situations and have various unmet medical needs. To provide appropriate solutions for these patients, an accurate understanding of their unmet medical needs is necessary. Patient-reported outcomes (PROs) reflect the problems of patients and are highly likely to be useful in understanding patient needs.

Epstein-Barr Virus-Induced 3 Attributes to TLR7-Mediated Splenomegaly.

Epstein-Barr virus-induced 3 (EBI3) functions as a component of the heterodimer cytokine IL-27, which regulates innate and acquired immune responses. The expression of EBI3 gene is induced by Toll-like receptors (TLRs). Repeated treatment with imiquimod (IMQ), a TLR7 agonist, induces splenomegaly and cytopaenia due to increased splenic function.

"Input/output cytokines" in epidermal keratinocytes and the involvement in inflammatory skin diseases.

Considering the role of epidermal keratinocytes, they occupy more than 90% of the epidermis, form a physical barrier, and also function as innate immune barrier. For example, epidermal keratinocytes are capable of recognizing various cytokines and pathogen-associated molecular pattern, and producing a wide variety of inflammatory cytokines, chemokines, and antimicrobial peptides. Previous basic studies have shown that the immune response of epidermal keratinocytes has a significant impact on inflammatory skin diseases.

Co-occurrence of non-alcoholic steatohepatitis exacerbates psoriasis associated with decreased adiponectin expression in a murine model.

Introduction: Clinical studies have suggested a bidirectional association between non-alcoholic steatohepatitis (NASH) and psoriasis, affecting each other's development and severity. Here, we explored bidirectional causal linkages between NASH and psoriasis using a murine model.

Methods: NASH was induced in mice by streptozotocin injection at 2 days of age and by high-fat diet feeding (STAM™ model).

TRAPS mutations in decrease the responsiveness to TNFα reduced cell surface expression of TNFR1.

Tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) is an autoinflammatory periodic fever syndrome associated with heterozygous mutations in , which encodes TNF receptor type I (TNFR1). Although possible proinflammatory mechanisms have been proposed, most previous studies were performed using overexpression models, which could lead to undesirable inflammatory responses due to artificial overexpression. It is crucial to reproduce heterozygous mutations at physiological expression levels; however, such studies remain limited.

Obesity and Dyslipidemia Synergistically Exacerbate Psoriatic Skin Inflammation.

Patients with psoriasis are frequently complicated with metabolic syndrome; however, it is not fully understood how obesity and dyslipidemia contribute to the pathogenesis of psoriasis. To investigate the mechanisms by which obesity and dyslipidemia exacerbate psoriasis using murine models and neonatal human epidermal keratinocytes (NHEKs), we used wild-type and -deficient dyslipidemic mice, and administered a high-fat diet for 10 weeks to induce obesity. Imiquimod was applied to the ear for 5 days to induce psoriatic dermatitis.

IL-17A promotes vascular calcification in an ex vivo murine aorta culture.

Background: Vascular calcification is characterized by mineral deposition in the vasculature, which is triggered by chronic systemic inflammation, including psoriasis. Psoriasis is an IL-17A-mediated inflammatory skin disease that is associated with exacerbated vascular calcification and high cardiovascular mortality. Although previous studies have shown that IL-17A induces vascular dysfunction in murine psoriasis models, it has not been clarified whether IL-17A induces vascular calcification.

Imatinib has minimal effects on inflammatory and osteopenic phenotypes in a murine cherubism model.

Objective: Cherubism is a genetic disorder characterised by bilateral jawbone deformation. The associated jawbone lesions regress after puberty, whereas severe cases require surgical treatment. Although several drugs have been tested, fundamental treatment strategies for cherubism have not been established.

Barium-induced pneumatosis intestinalis in a patient with anti-synthetase syndrome.

Pneumatosis intestinalis is defined as the presence of gas in the bowel wall. The combination of the two risks, pre-existing connective tissue diseases and barium contrast examination, may trigger pneumatosis intestinalis, albeit at a low incidence. Clinicians should be aware of the condition for proper differential diagnosis.

The "Ant-farm"-like Appearance of Restricted Lower Limb Vasculitis on Fluorodeoxyglucose-positron Emission Tomography.

Restricted lower limb vasculitis is a type of localized muscle vasculitis limited to the lower limbs. The usefulness of fluorodeoxyglucose-positron emission tomography (FDG-PET) for the diagnosis of this entity has not yet been reported. We herein report three patients with a fever and persistent lower limb pain.

Purple urine bags reflecting an aging society.

The purple urine bag syndrome is an underrecognized but quite common condition, resulting in marked discoloration of the urine bag system due to bacterial metabolism. This syndrome is associated with advanced age and bedridden persons.

SH3BP2 Deficiency Ameliorates Murine Systemic Lupus Erythematosus.

Background: The adaptor protein Src homology 3 domain-binding protein 2 (SH3BP2) is widely expressed in immune cells. It controls intracellular signaling pathways. The present study was undertaken to investigate the role of SH3BP2 in a murine systemic lupus erythematosus model.

Deletion of Exacerbates Lupus Nephritis by Targeting in Mice.

Objective: The micro RNAs (miRNAs) and their target mRNAs are differentially expressed in various immune-mediated cells. Here, we investigated the role of and sphingosine-1-phosphate receptor 1 () in the pathogenesis of systemic lupus erythematosus.

Methods: We analyzed miRNA and mRNA profiling data of CD4 splenic T cells derived from MRL/MpJ- /J mice.

Aortitis which developed after the administration of granulocyte-colony stimulating factor.

Drug-induced aortitis is rare; thus, the diagnosis of drug-induced aortitis could be delayed unless clinicians are aware of the disease entity. Herein, we describe the case of a 66-year-old woman who developed aortitis after administration of granulocyte-colony stimulating factor (G-CSF) during chemotherapy for her breast cancer. Thickening of the aortic wall was clearly detected by computed tomography (CT) and magnetic resonance imaging.

Inhibition of interleukin-6 signaling attenuates aortitis, left ventricular hypertrophy and arthritis in interleukin-1 receptor antagonist deficient mice.

The aim of the present study was to examine whether inhibition of Interleukin (IL)-6 signaling by MR16-1, an IL-6 receptor antibody, attenuates aortitis, cardiac hypertrophy, and arthritis in IL-1 receptor antagonist deficient (IL-1RA KO) mice. Four weeks old mice were intraperitoneally administered with either MR16-1 or non-immune IgG at dosages that were adjusted over time for 5 weeks. These mice were stratified into four groups: MR16-1 treatment groups, KO/MR low group (first 2.

Tattoo skin reaction as a skin manifestation of systemic sarcoidosis.

A 41-year-old man presented with itching of the skin surrounding his tattoos, blurred vision, fever, general fatigue, and arthralgia. Physical examination revealed skin bulges confined to the tattoo ink lines. Histological analyses of the skin revealed non-caseating granulomas surrounding the tattoo inks.

central venous catheter infection mimicking proteinase 3-antineutrophil cytoplasmic antibody (PR3-ANCA)-associated vasculitis.

A 40-year-old Japanese woman, who underwent total thyroidectomy, had suffered from repeated episodes of fever and microscopic hematuria for 3 years, which had started 3 months after central venous port catheter insertion. On admission, she had malaise and low-grade fever, and was found to have microscopic hematuria, urinary red blood cell casts, multiple pulmonary nodules, and positivity of proteinase 3-anti-neutrophil cytoplasmic antibody (PR3-ANCA), which were suggestive to the presence of ANCA-associated small vessel vasculitis. However, her blood culture and subsequent gene analysis revealed the positivity of , and she was diagnosed with bacteremia accompanying PR3-ANCA positivity.