ArticleJournal of immunology (Baltimore, Md. : 1950)2015
TAM receptor-dependent regulation of SOCS3 and MAPKs contributes to proinflammatory cytokine downregulation following chronic NOD2 stimulation of human macrophages.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- Axl and MerTK regulate synovial inflammation and are modulated by IL-6 inhibition in rheumatoid arthritis.Nature communications · 2024Article
- Review
- Gas6/Axl Axis Activation Dampens the Inflammatory Response in Osteoarthritic Fibroblast-like Synoviocytes and Synovial Explants.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Regulation of Immune Homeostasis via Muramyl Peptides-Low Molecular Weight Bioregulators of Bacterial Origin.Microorganisms · 2022Review
- Pattern Recognition Receptor Signaling and Cytokine Networks in Microbial Defenses and Regulation of Intestinal Barriers: Implications for Inflammatory Bowel Disease.Gastroenterology · 2022Review
- Guanxinkang Decoction Attenuates the Inflammation in Atherosclerosis by Regulating Efferocytosis and MAPKs Signaling Pathway in LDLRFrontiers in pharmacology · 2021Article
- How Inflammation Blunts Innate Immunity in Aging.Interdisciplinary topics in gerontology and geriatrics · 2020Review
- Gas6 Inhibits Toll-Like Receptor-Mediated Inflammatory Pathways in Mouse MicrogliaFrontiers in cellular neuroscience · 2020Article
- Selective Increment of Synovial Soluble TYRO3 Correlates with Disease Severity and Joint Inflammation in Patients with Rheumatoid Arthritis.Journal of immunology research · 2020Article
- Correlation of PD-L1 and SOCS3 Co-expression with the Prognosis of Hepatocellular Carcinoma Patients.Journal of Cancer · 2020Article
- STAT3 and STAT5 Signaling Thresholds Determine Distinct Regulation for Innate Receptor-Induced Inflammatory Cytokines, andJournal of immunology (Baltimore, Md. : 1950) · 2019Article
- Twist1 and Twist2 Induce Human Macrophage Memory upon Chronic Innate Receptor Treatment by HDAC-Mediated Deacetylation of Cytokine Promoters.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Crohn's disease IRGM risk alleles are associated with altered gene expression in human tissues.American journal of physiology. Gastrointestinal and liver physiology · 2019Article
- Fenretinide Inhibits Neutrophil Recruitment and IL-1β Production in Aspergillus fumigatus Keratitis.Cornea · 2018Article
- Age-related changes in expression and signaling of TAM receptor inflammatory regulators in monocytes.Oncotarget · 2018Article
- Targeting Gas6/TAM in cancer cells and tumor microenvironment.Molecular cancer · 2018Review
- Targeting Tyro3 ameliorates a model of PGRN-mutant FTLD-TDP via tau-mediated synaptic pathology.Nature communications · 2018Article
- E3 Ubiquitin ligase ZNRF4 negatively regulates NOD2 signalling and induces tolerance to MDP.Nature communications · 2017Article
- Suppressors of cytokine signaling: Potential immune checkpoint molecules for cancer immunotherapy.Cancer science · 2017Review
- The Role of TAM Family Receptors in Immune Cell Function: Implications for Cancer Therapy.Cancers · 2016Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Microbial-induced cytokine regulation is critical to intestinal immune homeostasis. Acute stimulation of nucleotide-binding oligomerization domain 2 (NOD2), the Crohn's disease-associated sensor of bacterial peptidoglycan, induces cytokines. However, cytokines are attenuated after chronic NOD2 and pattern recognition receptor stimulation of macrophages; similar attenuation is observed in intestinal macrophages. The role of Tyro3, Axl, and Mer (TAM) receptors in regulating chronic pattern recognition receptor stimulation and NOD2-induced outcomes has not been examined. Moreover, TAM receptors have been relatively less investigated in human macrophages. Whereas TAM receptors did not downregulate acute NOD2-induced cytokines in primary human macrophages, they were essential for downregulating signaling and proinflammatory cytokine secretion after chronic NOD2 and TLR4 stimulation. Axl and Mer were similarly required in mice for cytokine downregulation after chronic NOD2 stimulation in vivo and in intestinal tissues. Consistently, TAM expression was increased in human intestinal myeloid-derived cells. Chronic NOD2 stimulation led to IL-10- and TGF-β-dependent TAM upregulation in human macrophages, which, in turn, upregulated suppressor of cytokine signaling 3 expression. Restoring suppressor of cytokine signaling 3 expression under TAM knockdown conditions restored chronic NOD2-mediated proinflammatory cytokine downregulation. In contrast to the upregulated proinflammatory cytokines, attenuated IL-10 secretion was maintained in TAM-deficient macrophages upon chronic NOD2 stimulation. The level of MAPK activation in TAM-deficient macrophages after chronic NOD2 stimulation was insufficient to upregulate IL-10 secretion; however, full restoration of MAPK activation under these conditions restored c-Fos, c-Jun, musculoaponeurotic fibrosarcoma oncogene homolog K, and PU.1 binding to the IL-10 promoter and IL-10 secretion. Therefore, TAM receptors are critical for downregulating proinflammatory cytokines under the chronic NOD2 stimulation conditions observed in the intestinal environment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.