Therapeutic potential of interleukin-17 neutralization in a novel humanized mouse model of Sjögren's disease.

Sjögren's disease (SjD) is a chronic autoimmune disease, in which the immune system targets exocrine glands and leads to dryness symptoms. There is an increasing need to develop novel therapeutic approach as the treatment plan has not been changed in the past decade. However, findings in mouse model may not be directly applied in patients, given the substantial differences of immune system between human and mice.

Immunomodulatory effects of Yu-Ping-Feng formula on primary Sjögren syndrome: interrogating the T-cell response.

Ethnopharmacological treatments have shown beneficial effects in the clinical practice of autoimmune disorders. However, the underlying mechanism of immunomodulatory effects remains challenging, given the complicate composition of herbal medicines. Here, we developed an immunological approach to interrogate the T helper cell response.

Peroxynitrite reduces Treg cell expansion and function by mediating IL-2R nitration and aggravates multiple sclerosis pathogenesis.

T-helper 17 cells and regulatory T cells (Treg) are critical regulators in the pathogenesis of multiple sclerosis (MS) but the factors affecting Treg/Th17 balance remains largely unknown. Redox balance is crucial to maintaining immune homeostasis and reducing the severity of MS but the underlying mechanisms are unclear yet. Herein, we tested the hypothesis that peroxynitrite, a representative molecule of reactive nitrogen species (RNS), could inhibit peripheral Treg cells, disrupt Treg/Th17 balance and aggravate MS pathology by inducing nitration of interleukin-2 receptor (IL-2R) and down-regulating RAS/JNK-AP-1 signalling pathway.

The Future of Targeted Treatment of Primary Sjögren's Syndrome: A Focus on Extra-Glandular Pathology.

Primary Sjögren's syndrome (pSS) is a chronic, systemic autoimmune disease defined by exocrine gland hypofunction resulting in dry eyes and dry mouth. Despite increasing interest in biological therapies for pSS, achieving FDA-approval has been challenging due to numerous complications in the trials. The current literature lacks insight into a molecular-target-based approach to the development of biological therapies.

Aryl hydrocarbon receptor activation drives polymorphonuclear myeloid-derived suppressor cell response and efficiently attenuates experimental Sjögren's syndrome.

Myeloid-derived suppressor cells (MDSCs) comprise heterogeneous myeloid cell populations with immunosuppressive capacity that contribute to immune regulation and tolerance induction. We previously reported impaired MDSC function in patients with primary Sjögren's syndrome (pSS) and mice with experimental SS (ESS). However, the molecular mechanisms underlying MDSC dysfunction remain largely unclear.

Mitochondrial regulation of acute extrafollicular B-cell responses to COVID-19 severity.

Background: Patients with COVID-19 display a broad spectrum of manifestations from asymptomatic to life-threatening disease with dysregulated immune responses. Mechanisms underlying the detrimental immune responses and disease severity remain elusive.

Methods: We investigated a total of 137 APs infected with SARS-CoV-2.

Acteoside promotes B cell-derived IL-10 production and ameliorates autoimmunity.

IL-10-producing regulatory B (Breg) cells are well recognized for maintaining immune tolerance. The impaired Breg cell function with decreased IL-10-producing capacity has been found in autoimmune diseases, such as rheumatoid arthritis, lupus, and primary Sjogren's syndrome (pSS). However, seldom therapeutic agents targeting Breg cells are available to treat those autoimmune diseases.

Detection of T Follicular Helper Cells and T Follicular Regulatory Cells in Experimental Sjögren's Syndrome.

With the compiling studies on the autoimmune pathogenesis in the developing of Sjögren's syndrome, the functional importance of T follicular helper cells (Tfh) and T follicular regulatory cells (Tfr) was investigated, including our recent findings, among which various techniques for detecting Tfh and Tfr cells in Sjögren's syndrome have been reported. In this chapter, we describe detailed methods for the effective detection of Tfh and Tfr cells in mice with experimental Sjögren's syndrome (ESS), a mouse model with evident salivary hypofunction, increased serum levels of autoantibodies, and histopathological changes in the salivary glands. We provide representative detections of surface markers, cytokines, and transcription factors of Tfh and Tfr cells by flow cytometry and ELISpot assay.

Tetrahydroberberrubine attenuates lipopolysaccharide-induced acute lung injury by down-regulating MAPK, AKT, and NF-κB signaling pathways.

Acute lung injury (ALI) is a life-threatening syndrome that is characterized by overwhelming lung inflammation and increased microvascular permeability, which causes a high mortality worldwide. Here, we studied the protective effect of tetrahydroberberrubine (THBru), a berberine derivative, on a mouse model of lipopolysaccharide (LPS)-induced acute lung injury that was established in our previous studies. The results showed that a single oral administration of THBru significantly decreased the lung wet to dry weight (W/D) ratio at doses of 2, 10 and 50mg/kg administered 1h prior to LPS challenge (30mg/kg, intravenous injection).

Molecular mechanisms in lipopolysaccharide-induced pulmonary endothelial barrier dysfunction.

The confluent pulmonary endothelium plays an important role as a semi-permeable barrier between the vascular space of blood vessels and the underlying tissues, and it contributes to the maintenance of circulatory fluid homeostasis. Pulmonary endothelial barrier dysfunction is a pivotal early step in the development of a variety of high mortality diseases, such as acute lung injury (ALI). Endothelium barrier dysfunction in response to inflammatory or infectious mediators, including lipopolysaccharide (LPS), is accompanied by invertible cell deformation and interendothelial gap formation.

Advances in the pharmacological activities and mechanisms of diosgenin.

Diosgenin, a well-known steroid sapogenin derived from plants, has been used as a starting material for production of steroidal hormones. The present review will summarize published literature concerning pharmacological potential of diosgenin, and the underlying mechanisms of actions. Diosgenin has shown a vast range of pharmacological activities in preclinical studies.