CD163+ macrophages suppress T cell response by producing TGF-ß in pediatric colorectal polyps.

ABSTRACT

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 (Mϕ) were increased in colorectal polyps compared to the distal normal tissue from the same patients and the tissue from healthy donors. The frequency of Mϕwas 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 Mϕϕ from colorectal polyps compared to those from normal controls. Furthermore, real-time PCR revealed that TGF-ß, but not IL-10 and IL-4, was increased in colorectal polyps. Immunofluorescence and flow cytometry showed that TGF-ß was predominantly produced by CD163+Mϕ. In vitro experiments demonstrated that the supernatant from cultured polyps induced CD163 expression and TGF-ß production in blood-derived Mϕ. A co-culture experiment revealed that purified Mϕ from colorectal polyps suppressed T cell proliferation. Based on these results, we hypothesized that abundant CD163+Mϕ may promote the progression of colorectal polyps by inhibiting the local T cell response through TGF-ß production.