Cell-Bound TREM2, but not sTREM2 is Required for Macrophage Survival in vitro Caroline Burcham1, Hong Wang1, Forest Andrews1, Audrey McConnell1, Marcio Chedid1, David Riddell1, and Yaming Wang1 1Eli Lilly and Company
Genetic studies have demonstrated that altered function of Triggering receptor expressed on myeloid cells 2 (TREM2) is significantly associated with increased Alzheimer's disease (AD) risk. TREM2, a major activating receptor of microglia, is functionally involved in promoting survival and proliferation of microglia in vivo. Microglial surface TREM2 can be cleaved into a soluble form (sTREM2) via activities of metalloproteinases ADAM10 and ADAM17. To understand if sTREM2 plays a role in promoting cell survival and proliferation, we developed an in vitro model to assess the role of TREM2 in promoting survival of bone-marrow derived macrophages (BMDMs). By co-culturing wildtype and TREM2-/- BMDMs together, we were able to show that sTREM2 did not effectively rescue the survival defect of TREM2-/- BMDMs. Our data demonstrated that sTREM2 does not play a significant role in mediating survival of BMDMs but cell-bound TREM2 does. Although cell-bound TREM2 does enhance cell survival the question of whether sTREM2 has a physiological role remains unclear and requires further investigation.
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