ArticlePloS one2010
Loss of Jak2 selectively suppresses DC-mediated innate immune response and protects mice from lethal dose of LPS-induced septic shock.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 52 citations in OpenAlex.
- Unravelling the genetic and molecular basis of low-frequency rTMS induced changes in functional connectivity density in schizophrenia patients with auditory verbal hallucinations.Translational psychiatry · 2025Article
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- CTCF controls three-dimensional enhancer network underlying the inflammatory response of bone marrow-derived dendritic cells.Nature communications · 2023Article
- JAK2 gene knockout inhibits corneal allograft rejection in mice by regulating dendritic cell-induced T cell immune tolerance.Cell death discovery · 2022Article
- Article
- Aloperine Ameliorates IMQ-Induced Psoriasis by Attenuating Th17 Differentiation and Facilitating Their Conversion to Treg.Frontiers in pharmacology · 2022Article
- JAK2 deficiency improves erectile function in diabetic mice through attenuation of oxidative stress, apoptosis, and fibrosis.Andrology · 2021Article
- Loss of Jak2 protects cardiac allografts from chronic rejection by attenuating Th1 response along with increased regulatory T cells.American journal of translational research · 2019Article
- JAK/STAT Cytokine Signaling at the Crossroad of NK Cell Development and Maturation.Frontiers in immunology · 2019Review
- Dendritic Cells in Sepsis: Pathological Alterations and Therapeutic Implications.Journal of immunology research · 2017Review
- Chop Deficiency Protects Mice Against Bleomycin-induced Pulmonary Fibrosis by Attenuating M2 Macrophage Production.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- IL-6 Inhibition Reduces STAT3 Activation and Enhances the Antitumor Effect of Carboplatin.Mediators of inflammation · 2016Article
- Curcumin Suppressed Activation of Dendritic Cells via JAK/STAT/SOCS Signal in Mice with Experimental Colitis.Frontiers in pharmacology · 2016Article
- HMGB1 exacerbates bronchiolitis obliterans syndrome via RAGE/NF-κB/HPSE signaling to enhance latent TGF-β release from ECM.American journal of translational research · 2016Article
- Simultaneous inhibition of JAK and SYK kinases ameliorates chronic and destructive arthritis in mice.Arthritis research & therapy · 2015Article
- Immunological Consequences of JAK Inhibition: Friend or Foe?Current hematologic malignancy reports · 2015Review
- Cx3cr1 deficiency in mice attenuates hepatic granuloma formation during acute schistosomiasis by enhancing the M2-type polarization of macrophages.Disease models & mechanisms · 2015Article
- Carbon monoxide down-modulates Toll-like receptor 4/MD2 expression on innate immune cells and reduces endotoxic shock susceptibility.Immunology · 2015Article
- Translational initiation regulated by ATM in dendritic cells development.Cell death & disease · 2014Article
- T-cell costimulation protects obesity-induced adipose inflammation and insulin resistance.Diabetes · 2014Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Given the importance of Jak2 in cell signaling, a critical role for Jak2 in immune cells especially dendritic cells (DCs) has long been proposed. The exact function for Jak2 in DCs, however, remained poorly understood as Jak2 deficiency leads to embryonic lethality. Here we established Jak2 deficiency in adult Cre(+/+)Jak2(fl/fl) mice by tamoxifen induction. Loss of Jak2 significantly impaired DC development as manifested by reduced BMDC yield, smaller spleen size and reduced percentage of DCs in total splenocytes. Jak2 was also crucial for the capacity of DCs to mediate innate immune response. Jak2(-/-) DCs were less potent in response to inflammatory stimuli and showed reduced capacity to secrete proinflammatory cytokines such as TNFalpha and IL-12. As a result, Jak2(-/-) mice were defective for the early clearance of Listeria after infection. However, their potency to mediate adaptive immune response was not affected. Unlike DCs, Jak2(-/-) macrophages showed similar capacity secretion of proinflammatory cytokines, suggesting that Jak2 selectively modulates innate immune response in a DC-dependent manner. Consistent with these results, Jak2(-/-) mice were remarkably resistant to lethal dose of LPS-induced septic shock, a deadly sepsis characterized by the excessive innate immune response, and adoptive transfer of normal DCs restored their susceptibility to LPS-induced septic shock. Mechanistic studies revealed that Jak2/SATA5 signaling is pivotal for DC development and maturation, while the capacity for DCs secretion of proinflammatory cytokines is regulated by both Jak2/STAT5 and Jak2/STAT6 signaling.
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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.