Neuronal, stromal, and T-regulatory cell crosstalk in murine skeletal muscle.
Kathy WangOmar K YaghiRaul German SpallanzaniXin ChenDavid ZemmourNicole LaiIsaac M ChiuChristophe BenoistDiane MathisPublished in: Proceedings of the National Academy of Sciences of the United States of America (2020)
A distinct population of Foxp3+CD4+ regulatory T (Treg) cells promotes repair of acutely or chronically injured skeletal muscle. The accumulation of these cells depends critically on interleukin (IL)-33 produced by local mesenchymal stromal cells (mSCs). An intriguing physical association among muscle nerves, IL-33+ mSCs, and Tregs has been reported, and invites a deeper exploration of this cell triumvirate. Here we evidence a striking proximity between IL-33+ muscle mSCs and both large-fiber nerve bundles and small-fiber sensory neurons; report that muscle mSCs transcribe an array of genes encoding neuropeptides, neuropeptide receptors, and other nerve-related proteins; define muscle mSC subtypes that express both IL-33 and the receptor for the calcitonin-gene-related peptide (CGRP); and demonstrate that up- or down-tuning of CGRP signals augments or diminishes, respectively, IL-33 production by muscle mSCs and later accumulation of muscle Tregs. Indeed, a single injection of CGRP induced much of the genetic program elicited in mSCs early after acute skeletal muscle injury. These findings highlight neural/stromal/immune-cell crosstalk in tissue repair, suggesting future therapeutic approaches.
Keyphrases
- skeletal muscle
- mesenchymal stem cells
- insulin resistance
- umbilical cord
- bone marrow
- induced apoptosis
- genome wide
- single cell
- cell therapy
- stem cells
- transcription factor
- regulatory t cells
- dna methylation
- physical activity
- mental health
- immune response
- high resolution
- copy number
- type diabetes
- mass spectrometry
- drug induced
- quality improvement
- brain injury
- dendritic cells
- stress induced
- cell death
- cerebral ischemia
- genome wide identification