Experimental Colitis Enhances Temporal Variations in CX3CR1 Cell Colonization of the Gut and Brain Following Irradiation

Ayush Batra, Triet M. Bui, Jacob F. Rehring, Lenore K. Yalom, William A. Muller, David P. Sullivan, Ronen Sumagin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Peripheral monocyte-derived CX3C chemokine receptor 1 positive (CX3CR1+) cells play important roles in tissue homeostasis and gut repopulation. Increasing evidence also supports their role in immune repopulation of the brain parenchyma in response to systemic inflammation. Adoptive bone marrow transfer from CX3CR1 fluorescence reporter mice and high-resolution confocal microscopy was used to assess the time course of CX3CR1+ cell repopulation of steady-state and dextran sodium sulfate (DSS)-inflamed small intestine/colon and the brain over 4 weeks after irradiation. CX3CR1+ cell colonization and morphologic polarization into fully ramified cells occurred more rapidly in the small intestine than in the colon. For both organs, the crypt/mucosa was more densely populated than the serosa/muscularis layer, indicating preferential temporal and spatial occupancy. Repopulation of the brain was delayed compared with that of gut tissue, consistent with the immune privilege of this organ. However, DSS-induced colon injury accelerated the repopulation. Expression analyses confirmed increased chemokine levels and macrophage colonization within the small intestine/colon and the brain by DSS-induced injury. Early increases of transmembrane protein 119 and ionized calcium binding adaptor molecule 1 expression within the brain after colon injury suggest immune-priming effect of brain resident microglia in response to systemic inflammation. These findings identify temporal differences in immune repopulation of the gut and brain in response to inflammation and show that gut inflammation can impact immune responses within the brain.

Original languageEnglish (US)
Pages (from-to)295-307
Number of pages13
JournalAmerican Journal of Pathology
Volume192
Issue number2
DOIs
StatePublished - Feb 2022

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint

Dive into the research topics of 'Experimental Colitis Enhances Temporal Variations in CX3CR1 Cell Colonization of the Gut and Brain Following Irradiation'. Together they form a unique fingerprint.

Cite this