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Published on: May 31, 2018
The PSMP-CCR2 interactions trigger monocyte/macrophage-dependent colitis
Xiaolei Pei1,2, Danfeng Zheng1, Shaoping She1
1Department of Immunology, School of Basic Medical Sciences, and Key Laboratory of Medical Immunology of Ministry of Health, Peking University Health Science Center, Beijing, 100191, P.R. China.
Abstract:
Monocytes/macrophages have been found to be an important component of colitis. However, the key chemokine that initiates the CCR2+ monocytes migration from circulation to colitis tissue remains to be undiscovered. PC3-secreted microprotein (PSMP) is a novel chemokine whose receptor is CCR2. The physiological and pathological functions of PSMP have not yet been reported. In this study, PSMP was found to be expressed in colitis and colonic tumor tissues from patients and significantly up-regulated in mouse DSS-induced colitis tissues. PSMP overexpression in the colon aggravated the DSS-induced colitis and the anti-PSMP neutralizing antibody mollified the colitis by reducing macrophage infiltration and inhibiting the expression of IL-6, TNF-α and CCL2. Furthermore, we demonstrated that lipopolysaccharide and muramyl dipeptide induced PSMP expression in the colonic epithelial cells. PSMP was up-regulated in the initial stage prior to IL-6, TNF-α and CCL2 up-regulated expression in DSS colitis and promoted the M1 macrophages to produce CCL2. PSMP chemo-attracted Ly6Chi monocytes in a CCR2 dependent manner via in situ chemotaxis and adoptive transfer assays. Our data identify PSMP as a key molecule in ulcerative colitis, which provides a novel mechanism of monocyte/macrophage migration that affects gut innate immunity and makes PSMP a potential target for controlling colitis.
Insights
PC3-secreted microprotein (PSMP) is identified as a key chemokine in ulcerative colitis, driving monocyte migration to inflamed gut tissues. Targeting PSMP offers a novel therapeutic strategy for managing colitis and related inflammatory conditions.
Area of Science:
- Immunology
- Gastroenterology
- Molecular Biology
Background:
- Monocytes and macrophages are crucial in colitis pathogenesis.
- The specific chemokine initiating monocyte migration to colitis tissue is unknown.
Purpose of the Study:
- To identify the key chemokine responsible for monocyte migration in colitis.
- To investigate the role of PC3-secreted microprotein (PSMP) in colitis.
Main Methods:
- Analysis of PSMP expression in human and mouse colitis and tumor tissues.
- Investigating the effect of PSMP overexpression and anti-PSMP antibodies in DSS-induced colitis models.
- Assessing PSMP's role in monocyte chemoattraction using chemotaxis and adoptive transfer assays.
Main Results:
- PSMP is upregulated in colitis tissues and its overexpression exacerbates disease.
- Anti-PSMP antibodies reduce inflammation by decreasing macrophage infiltration and key cytokine expression (IL-6, TNF-α, CCL2).
- PSMP chemoattracts monocytes in a CCR2-dependent manner and promotes M1 macrophage CCL2 production.
Conclusions:
- PSMP is a critical chemokine in ulcerative colitis, mediating monocyte/macrophage recruitment.
- PSMP represents a novel mechanism influencing gut innate immunity.
- PSMP is a potential therapeutic target for controlling colitis.
