Leukocyte-associated immunoglobulin-like receptor 1 inhibits T-cell signaling by decreasing protein phosphorylation in the T-cell signaling pathway Signal Transduction

Multiple observations implicate T-cell dysregulation as a central event in the pathogenesis of rheumatoid arthritis. Here, we investigated mechanisms for suppressing T-cell activation via the inhibitory receptor leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1). To determine how LAIR-1 affects T-cell receptor (TCR) signaling, we compared 1) T cells from LAIR-1–sufficient and –deficient mice, 2) Jurkat cells expressing either LAIR-1 mutants or C-terminal Src kinase (CSK) mutants, and 3) T cells from mice that contain a CSK transgene susceptible to chemical inhibition. Our results indicated that LAIR-1 engagement by collagen or by complement C1q (C1Q, which contains a collagen-like domain) inhibits TCR signaling by decreasing the phosphorylation of key components in the canonical T-cell signaling pathway, including LCK proto-oncogene SRC family tyrosine kinase (LCK), LYN proto-oncogene SRC family tyrosine kinase (LYN), ζ chain of T-cell receptor–associated protein kinase 70 (ZAP-70), and three mitogen-activated protein kinases (extracellular signal–regulated kinase, c-Jun N-terminal kinase 1/2, and p38). The intracellular region of LAIR-1 contains two immunoreceptor tyrosine-based inhibition motifs that are both phosphorylated by LAIR-1 activation, and immunoprecipitation experiments revealed that Tyr-251 in LAIR-1 binds CSK. Using CRISPR/Cas9-mediated genome editing, we demonstrate that CSK is essential for the LAIR-1–induced inhib...
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Molecular Bases of Disease Source Type: research

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ConclusionIntense dust cloud exposure among responders and PTSD among community members were associated with a statistically significant increased risk of new ‐onset systemic autoimmune disease. Clinicians treating 9/11 survivors should be aware of the potential increased risk of systemic autoimmune disease in this population.
Source: Arthritis and Rheumatology - Category: Rheumatology Authors: Tags: Original Article Source Type: research
Conclusion: Our study suggested that quercetin suppresses the migration and invasion of FLSs via regulating the miR-146a/GATA6 axis. PMID: 32216502 [PubMed - as supplied by publisher]
Source: Immunopharmacology and Immunotoxicology - Category: Allergy & Immunology Tags: Immunopharmacol Immunotoxicol Source Type: research
  Cannabis, weed, marijuana, pot. It goes by several names, but we all know what it smells like. As weed becomes more mainstream, we on the Not Crazy podcast want to know: Is marijuana really an effective treatment for anxiety? Is it just a coping mechanism? Or a vice? In today’s podcast, Gabe and Jackie look at the research and weigh out the evidence. They also interview Eileen Davidson, a rheumatoid arthritis patient who regularly uses marijuana as a medicine to see what she has to say. What’s your take? Tune in for an open-minded discussion about weed. (Transcript Available Below) SUBSCRIBE &REV...
Source: World of Psychology - Category: Psychiatry & Psychology Authors: Tags: Anxiety and Panic General Medications Not Crazy Podcast Source Type: blogs
Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovitis. Pien Tze Huang (PZH) is a Chinese patent medicine with anti-inflammatory and immunomodulatory effects. However, whether PZH could ...
Source: Chinese Medicine - Category: Complementary Medicine Authors: Tags: Research Source Type: research
This study, for the first time, shows that transplantation of non-autologous mitochondria from healthy skeletal muscle cells into normal cardiomyocytes leads to short-term improvement of bioenergetics indicating "supercharged" state. However, over time these improved effects disappear, which suggests transplantation of mitochondria may have a potential application in settings where there is an acute stress. Outlining Some of the Science Behind Partial Reprogramming at Turn.bio https://www.fightaging.org/archives/2020/03/outlining-some-of-the-science-behind-partial-reprogramming-at-turn-bio/ Tur...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Purpose of review This review summarizes the current evidence on treatment strategies for inflammatory arthritis because of cancer treatment with immune checkpoint inhibitors (ICI), prognosis of ICI-induced arthritis, and management of patients with preexisting inflammatory arthritis receiving ICI therapy. Recent findings Inflammatory arthritis is the most common rheumatic immune-related adverse event observed in patients receiving ICI therapy. Most patients can successfully be treated with low doses of corticosteroids or conventional synthetic disease modifying anti-rheumatic drugs (DMARDs). A small minority will dev...
Source: Current Opinion in Rheumatology - Category: Rheumatology Tags: RHEUMATOID ARTHRITIS: Edited by Joshua F. Baker Source Type: research
AbstractThe dysregulation of the JAK –STAT pathway is associated with various immune disorders. Four JAK inhibitors have been approved for rheumatoid arthritis (RA), and numerous JAK inhibitors are currently being tested in phase II and III trials for the treatment of various autoimmune inflammatory diseases. In this narrative review , we elucidate the involvement of the JAK–STAT signaling pathway in the pathogenesis of connective tissue diseases (CTDs). We also discuss the efficacy of the first- and second-generation JAK inhibitors (tofacitinib, baricitinib, ruxolitinib, peficitinib, filgotinib, upadacitinib, ...
Source: Clinical Reviews in Allergy and Immunology - Category: Allergy & Immunology Source Type: research
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Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
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Source: TIME: Health - Category: Consumer Health News Authors: Tags: Uncategorized COVID-19 feature Londontime Source Type: news
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and joint stiffness, finally leading to tissue destruction. Connective tissue growth factor (CTGF) is a critical factor i...
Source: Arthritis Research and Therapy - Category: Rheumatology Authors: Tags: Research article Source Type: research
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