Analysis of the immune response to sciatic nerve injury identifies efferocytosis as a key mechanism of nerve debridement.

Autor:	Kalinski AL; Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States., Yoon C; Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States., Huffman LD; 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., Duncker PC; Department of Neurology, University of Michigan Medical School, Ann Arbor, United States., Kohen R; 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., Passino R; Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States., Hafner H; Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States., Johnson C; Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States., Kawaguchi R; Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States., Carbajal KS; Department of Neurology, University of Michigan Medical School, Ann Arbor, United States., Jara JS; Burke Neurological Institute, White Plains, United States., Hollis E; Burke Neurological Institute, White Plains, United States.; The Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, United States., Geschwind DH; Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States., Segal BM; Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, United States.; The Neurological Institute, The Ohio State University, Columbus, United States., Giger RJ; 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.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2020 Dec 02; Vol. 9. Date of Electronic Publication: 2020 Dec 02.
DOI:	10.7554/eLife.60223
Abstrakt:	Sciatic nerve crush injury triggers sterile inflammation within the distal nerve and axotomized dorsal root ganglia (DRGs). Granulocytes and pro-inflammatory Ly6C high monocytes infiltrate the nerve first and rapidly give way to Ly6C negative 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 Interests: AK, CY, LH, PD, RK, RP, HH, CJ, RK, KC, JJ, EH, DG, BS, RG No competing interests declared (© 2020, Kalinski et al.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu