| First Author | Yaghi OK | Year | 2023 |
| Journal | Nat Immunol | Volume | 24 |
| Issue | 12 | Pages | 2053-2067 |
| PubMed ID | 37932455 | Mgi Jnum | J:358285 |
| Mgi Id | MGI:7778521 | Doi | 10.1038/s41590-023-01669-w |
| Citation | Yaghi OK, et al. (2023) A discrete 'early-responder' stromal-cell subtype orchestrates immunocyte recruitment to injured tissue. Nat Immunol 24(12):2053-2067 |
| abstractText | Following acute injury, stromal cells promote tissue regeneration by a diversity of mechanisms. Time-resolved single-cell RNA sequencing of muscle mesenchymal stromal cells (MmSCs) responding to acute injury identified an 'early-responder' subtype that spiked on day 1 and expressed a notable array of transcripts encoding immunomodulators. IL-1beta, TNF-alpha and oncostatin M each strongly and rapidly induced MmSCs transcribing this immunomodulatory program. Macrophages amplified the program but were not strictly required for its induction. Transfer of the inflammatory MmSC subtype, tagged with a unique surface marker, into healthy hindlimb muscle induced inflammation primarily driven by neutrophils and macrophages. Among the abundant inflammatory transcripts produced by this subtype, Cxcl5 was stroma-specific and highly upregulated with injury. Depletion of this chemokine early after injury revealed a substantial impact on recruitment of neutrophils, a prolongation of inflammation to later times and an effect on tissue regeneration. Mesenchymal stromal cell subtypes expressing a comparable inflammatory program were found in a mouse model of muscular dystrophy and in several other tissues and pathologies in both mice and humans. These 'early-responder' mesenchymal stromal cells, already in place, permit rapid and coordinated mobilization and amplification of critical cell collaborators in response to injury. |
