6533b86ffe1ef96bd12cd438
RESEARCH PRODUCT
Genetic Cell Ablation Reveals Clusters of Local Self-Renewing Microglia in the Mammalian Central Nervous System
Julia BruttgerEmmanuel PinteauxTommy RegenYochai WolfNicola HoppmannAri WaismanHarald BinderWerner MüllerKhalad KarramMarco PrinzTobias BoppMatthias KleinFederico MariniSimone WörtgeMatthias MackFrauke ZippThomas BlankSimon YonaSteffen Jungsubject
Central Nervous SystemCellular differentiationCentral nervous systemInterleukin-1betaImmunologyCX3C Chemokine Receptor 1Bone Marrow CellsBiologyMiceCell MovementCX3CR1medicineAnimalsImmunology and AllergyProgenitor cellNeuroinflammationCell ProliferationReceptors Interleukin-1 Type IMicrogliaBase SequenceTumor Necrosis Factor-alphaMacrophagesCell DifferentiationSequence Analysis DNAHematopoietic Stem CellsCell biologyMice Inbred C57BLmedicine.anatomical_structureInfectious DiseasesImmunologyTumor necrosis factor alphaReceptors ChemokineMicrogliaSignal transductionSignal Transductiondescription
SummaryDuring early embryogenesis, microglia arise from yolk sac progenitors that populate the developing central nervous system (CNS), but how the tissue-resident macrophages are maintained throughout the organism’s lifespan still remains unclear. Here, we describe a system that allows specific, conditional ablation of microglia in adult mice. We found that the microglial compartment was reconstituted within 1 week of depletion. Microglia repopulation relied on CNS-resident cells, independent from bone-marrow-derived precursors. During repopulation, microglia formed clusters of highly proliferative cells that migrated apart once steady state was achieved. Proliferating microglia expressed high amounts of the interleukin-1 receptor (IL-1R), and treatment with an IL-1R antagonist during the repopulation phase impaired microglia proliferation. Hence, microglia have the potential for efficient self-renewal without the contribution of peripheral myeloid cells, and IL-1R signaling participates in this restorative proliferation process.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-07-21 | Immunity |