Enteric Glia Modulate Macrophage Phenotype and Visceral Sensitivity following Inflammation

Vladimir Grubišić, Jonathon Lee McClain, David E Fried, Iveta S Grants, Pradeep Rajasekhar, Eva Csizmadia, Olujimi A Ajijola, Ralph E Watson, Daniel P. Poole, Simon Christopher Robson, Fievos Leontiou Christofi

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Mechanisms resulting in abdominal pain include altered neuro-immune interactions in the gastrointestinal tract, but the signaling processes that link immune activation with visceral hypersensitivity are unresolved. We hypothesized that enteric glia link the neural and immune systems of the gut and that communication between enteric glia and immune cells modulates the development of visceral hypersensitivity. To this end, we manipulated a major mechanism of glial intercellular communication that requires connexin-43 and assessed the effects on acute and chronic inflammation, visceral hypersensitivity, and immune responses. Deleting connexin-43 in glia protected against the development of visceral hypersensitivity following chronic colitis. Mechanistically, the protective effects of glial manipulation were mediated by disrupting the glial-mediated activation of macrophages through the macrophage colony-stimulating factor. Collectively, our data identified enteric glia as a critical link between gastrointestinal neural and immune systems that could be harnessed by therapies to ameliorate abdominal pain.
Original languageEnglish
Article number108100
Number of pages25
JournalCell Reports
Volume32
Issue number10
DOIs
Publication statusPublished - 8 Sep 2020

Cite this

Grubišić, V., McClain, J. L., Fried, D. E., Grants, I. S., Rajasekhar, P., Csizmadia, E., Ajijola, O. A., Watson, R. E., Poole, D. P., Robson, S. C., & Christofi, F. L. (2020). Enteric Glia Modulate Macrophage Phenotype and Visceral Sensitivity following Inflammation. Cell Reports, 32(10), [108100]. https://doi.org/10.1016/j.celrep.2020.108100