PCBP1 acts as a regulator of CCL2 expression in macrophages to induce recruitment of monocyte-derived macrophages into the inflamed colon

Abstract Intestinal macrophages with functional plasticity play essential roles in gut immune responses by increasing chemokines and cytokines, thereby contributing to the pathogenesis of inflammatory bowel disease (IBD). Poly(rC)-binding protein 1 (PCBP1), which is widely expressed in immune cells,...

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Bibliographic Details
Published in:International immunology 2023-05, Vol.35 (6), p.287-299
Main Authors: Yang, Xinquan, Yabe-Wada, Toshiki, Han, Jia, Saito, Fumiji, Ogasawara, Chie, Yamada, Sohsuke, Onai, Nobuyuki
Format: Article
Language:English
Subjects:
Animals
Chemokines
Colitis
Colon
Cytokines - metabolism
Dextran Sulfate - pharmacology
Inflammatory Bowel Diseases
Ligands
Macrophages
Mice
Mice, Inbred C57BL
RNA, Messenger - metabolism
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Summary:Abstract Intestinal macrophages with functional plasticity play essential roles in gut immune responses by increasing chemokines and cytokines, thereby contributing to the pathogenesis of inflammatory bowel disease (IBD). Poly(rC)-binding protein 1 (PCBP1), which is widely expressed in immune cells, binds to nucleic acids in mRNA processing, stabilization, translation and transcription. However, little is known about the influence of PCBP1 on macrophages and its specific mechanism in inflamed intestines. In this study, conditional depletion of Pcbp1 in macrophages protected mice from progression of dextran sulfate sodium induced colitis and resulted in significant alleviation of colitis. Pcbp1 deficiency markedly decreased C-C motif chemokine ligand 2 (CCL2) production by colonic CX3C motif chemokine receptor 1+ (CX3CR1+) macrophages and reduced accumulation of pro-inflammatory macrophages and production of pro-inflammatory cytokines, such as IL-6 and TNF-α, in the inflamed colon. RNA-immunoprecipitation analysis indicated that PCBP1 might interact with Ccl2 mRNA and regulate its expression in macrophages. PCBP1 expression in inflamed intestines also correlated significantly with IBD severity in patients, suggesting a critical involvement of PCBP1 in intestinal inflammation. We anticipate that our findings will facilitate the development of novel therapeutic approaches for IBD by targeting the specific function of immune cells in the local microenvironment, thereby helping to reduce adverse effects. PCBP1 is crucial for the development of colitis Graphical Abstract Graphical Abstract
ISSN:1460-2377
1460-2377
DOI:10.1093/intimm/dxad003