PT  - JOURNAL ARTICLE
AU  - Ashley L. Kalinski
AU  - Choya Yoon
AU  - Lucas D. Huffman
AU  - Patrick C. Duncker
AU  - Rafi Kohen
AU  - Ryan Passino
AU  - Hannah Hafner
AU  - Craig Johnson
AU  - Riki Kawaguchi
AU  - Kevin S. Carbajal
AU  - Juan Sebastián Jara
AU  - Edmund Hollis
AU  - Daniel H. Geschwind
AU  - Benjamin M. Segal
AU  - Roman J. Giger
TI  - Analysis of the Immune Response to Sciatic Nerve Injury Identifies Efferocytosis as a Key Mechanism of Nerve Debridement
AID  - 10.1101/2020.10.23.352872
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.10.23.352872
4099  - http://biorxiv.org/content/early/2020/10/24/2020.10.23.352872.short
4100  - http://biorxiv.org/content/early/2020/10/24/2020.10.23.352872.full
AB  - 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.Competing Interest StatementThe authors have declared no competing interest.