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TREM2 Improves Animal Model of MS

Discussion in 'Other Health News and Research' started by aprilk1869, Jan 10, 2012.

  1. aprilk1869

    aprilk1869 Senior Member

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    This is comparatively old news however I've not been able to find any info regarding TREM2 here so I thought it would be interesting. If I understand correctly, it's made in the bone marrow and then crosses the blood brain barrier to clear away cellular debris.

    I was wondering whether simply eating bone marrow would be able to provide this, I know that bone broths are considered to be very healing in general. Apparently Terry Wahls drinks bone broth every day.


    TREM2-Transduced Myeloid Precursors Mediate Nervous Tissue Debris Clearance and Facilitate Recovery in an Animal Model of Multiple Sclerosis

    Background


    In multiple sclerosis, inflammation can successfully be prevented, while promoting repair is still a major challenge. Microglial cells, the resident phagocytes of the central nervous system (CNS), are hematopoietic-derived myeloid cells and express the triggering receptor expressed on myeloid cells 2 (TREM2), an innate immune receptor. Myeloid cells are an accessible source for ex vivo gene therapy. We investigated whether myeloid precursor cells genetically modified to express TREM2 affect the disease course of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis.

    Methods and Findings

    EAE was induced in mice by immunization with a myelin autoantigen. Intravenous application of TREM2-transduced bone marrowderived myeloid precursor cells at the EAE peak led to an amelioration of clinical symptoms, reduction in axonal damage, and prevention of further demyelination. TREM2-transduced myeloid cells applied intravenously migrated into the inflammatory spinal cord lesions of EAE-diseased mice, showed increased lysosomal and phagocytic activity, cleared degenerated myelin, and created an anti-inflammatory cytokine milieu within the CNS.

    Conclusions

    Intravenously applied bone marrowderived and TREM2-tranduced myeloid precursor cells limit tissue destruction and facilitate repair within the murine CNS by clearance of cellular debris during EAE. TREM2 is a new attractive target for promotion of repair and resolution of inflammation in multiple sclerosis and other neuroinflammatory diseases.

    Full paper: http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0040124
     
  2. aprilk1869

    aprilk1869 Senior Member

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    IL-10 Suppresses Calcium-Mediated Costimulation of Receptor Activator NF-?B Signaling during Human Osteoclast Differentiation by Inhibiting TREM-2 Expression

    Induction of effective osteoclastogenesis by RANK (receptor activator of NF-?B) requires costimulation by ITAM-coupled receptors. In humans, the TREM-2 (triggering receptor expressed on myeloid cells 2) ITAM-coupled receptor plays a key role in bone remodeling, as patients with TREM-2 mutations exhibit defective osteoclastogenesis and bone lesions. We have identified a new rapidly induced costimulatory pathway for RANK signaling that is dependent on TREM-2 and mediated by calcium signaling. TREM-2-dependent calcium signals are required for RANK-mediated activation of calcium/calmodulin-dependent protein kinase (CaMK)II and downstream MEK and ERK MAPKs that are important for osteoclastogenesis. IL-10 inhibited RANK-induced osteoclastogenesis and selectively inhibited calcium signaling downstream of RANK by inhibiting transcription of TREM-2. Down-regulation of TREM-2 expression resulted in diminished RANKL-induced activation of the CaMK-MEK-ERK pathway and decreased expression of the master regulator of osteoclastogenesis NFATc1. These findings provide a new mechanism of inhibition of human osteoclast differentiation. The results also yield insights into crosstalk between ITAM-coupled receptors and heterologous receptors such as RANK, and they identify a mechanism by which IL-10 can suppress cellular responses to TNFR family members.

    http://www.jimmunol.org/content/183/4/2444.short
     

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