Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States
Choya Yoon
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States
Lucas D Huffman
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States; Neuroscience Graduate Program, University of Michigan Medical School, Ann Arbor, United States
Patrick C Duncker
Department of Neurology, University of Michigan Medical School, Ann Arbor, United States
Rafi Kohen
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States; Neuroscience Graduate Program, University of Michigan Medical School, Ann Arbor, United States
Ryan Passino
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States
Hannah Hafner
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States
Craig Johnson
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States
Riki Kawaguchi
Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States
Kevin S Carbajal
Department of Neurology, University of Michigan Medical School, Ann Arbor, United States
Juan Sebastian Jara
Burke Neurological Institute, White Plains, United States
Burke Neurological Institute, White Plains, United States; The Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, United States
Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States
Benjamin M Segal
Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, United States; The Neurological Institute, The Ohio State University, Columbus, United States
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States; Neuroscience Graduate Program, University of Michigan Medical School, Ann Arbor, United States; Department of Neurology, University of Michigan Medical School, Ann Arbor, United States
Sciatic nerve crush injury triggers sterile inflammation within the distal nerve and axotomized dorsal root ganglia (DRGs). Granulocytes and pro-inflammatory Ly6Chigh monocytes infiltrate the nerve first and rapidly give way to Ly6Cnegative inflammation-resolving macrophages. In axotomized DRGs, few hematogenous leukocytes are detected and resident macrophages acquire a ramified morphology. Single-cell RNA-sequencing of injured sciatic nerve identifies five macrophage subpopulations, repair Schwann cells, and mesenchymal precursor cells. Macrophages at the nerve crush site are molecularly distinct from macrophages associated with Wallerian degeneration. In the injured nerve, macrophages ‘eat’ apoptotic leukocytes, a process called efferocytosis, and thereby promote an anti-inflammatory milieu. Myeloid cells in the injured nerve, but not axotomized DRGs, strongly express receptors for the cytokine GM-CSF. In GM-CSF-deficient (Csf2-/-) mice, inflammation resolution is delayed and conditioning-lesion-induced regeneration of DRG neuron central axons is abolished. Thus, carefully orchestrated inflammation resolution in the nerve is required for conditioning-lesion-induced neurorepair.
