期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 96, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.intimp.2021.107644
关键词
Colorectal polyps; CD163; Macrophage; TGF-beta; T cell
资金
- National Natural Science Foundation of China [81770552, 81801571]
- Postdoctoral Science Foundation of China [2020T130131]
- Development Project of Foshan Fourth People's Hospital [FSSYKF-2020017]
- Guangdong Natural Science Foundation [2017ZC0333]
- Clinical key specialty and construction of cultivate the key subject of Guangzhou Women and Children's Medical Center [170000105]
- Guangzhou Women and Children's Medical Center [201704020223]
- Funding of Guangzhou Institute of Pediatrics/Guangzhou Women and Children's Medical Center [IP2019010]
- Sun YatSen University [201704020223]
The study revealed that CD163(+)M phi in colorectal polyps may promote polyp progression by inhibiting the local T cell response.
The local immune response plays an important role in the pathogenesis of colorectal carcinoma. Patients with colorectal polyps are at increased risk of colorectal cancer. However, the immunoregulation of early-stage colorectal polyps remain unknown. In the study, 202 biopsy samples from 80 pediatric patients with colorectal polyps and from 42 normal controls were collected. We found that the number of CD4(+), CD8(+)T cells and CD19(+)B cells were reduced, whereas CD68(+) macrophages (M phi) were increased in colorectal polyps compared to the distal normal tissue from the same patients and the tissue from healthy donors. The frequency of M phi was negatively correlated with the number of CD4(+) and CD8(+)T cells but not CD19(+)B cells in colorectal polyps. We further identified that CD163 was highly expressed on M phi phi from colorectal polyps compared to those from normal controls. Furthermore, real-time PCR revealed that TGF-beta, but not IL-10 and IL-4, was increased in colorectal polyps. Immunofluorescence and flow cytometry showed that TGF-beta was predominantly produced by CD163(+)M phi. In vitro experiments demonstrated that the supernatant from cultured polyps induced CD163 expression and TGF-beta production in blood-derived M phi. A co-culture experiment revealed that purified M phi from colorectal polyps suppressed T cell proliferation. Based on these results, we hypothesized that abundant CD163(+)M phi may promote the progression of colorectal polyps by inhibiting the local T cell response through TGF-beta production.
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