CD19 lo CD27 hi Plasmablasts Suppress Harmful Th17 Inflammation Through Interleukin 10 Pathway in Colorectal Cancer

• Published in: DNA and cell biology Vol. 36; no. 10; p. 870
• Main Authors: Mao, Hui, Pan, Fei, Wu, Zhiyong, Wang, Zhikuan, Zhou, Yanhua, Zhang, Pengfei, Gou, Miaomiao, Dai, Guanghai
• Format: Journal Article
• Language: English
• Published: United States 01.10.2017
• Subjects: Antigens, CD19 - immunology; B-Lymphocytes, Regulatory - immunology; CD4-Positive T-Lymphocytes - metabolism; Colorectal Neoplasms - metabolism; Humans; Inflammation - immunology; Inflammation - pathology; Interleukin-10 - metabolism; Interleukin-17 - immunology; Plasma Cells - metabolism; T-Lymphocytes, Regulatory - immunology; Th17 Cells - immunology; Tumor Necrosis Factor Receptor Superfamily, Member 7 - immunology; immune response; plasmablast; colorectal cancer
• ISSN: 1557-7430
• DOI: 10.1089/dna.2017.3814

The enrichment of CD20 and CD138 immune cells were previously associated with improved survival in colorectal cancer (CRC). We previously discovered that the resected tumors in CRC patients were highly enriched with interleukin (IL)-10-producing CD19 CD27 plasmablasts with potential suppressor functions. It is still unknown what roles the CD19 CD27 plasmablasts play in CRC patients. In this study, we first demonstrated that B cells from peripheral blood mononuclear cells (PBMCs) could be stimulated to resemble tumor-infiltrating plasmablasts using a coculture containing Caco-2 and heat-killed bacteria. The PBMC-derived CD19 CD27 plasmablasts and tumor-infiltrating plasmablasts contained comparable frequencies of IL-10-expressing cells and secreted similar levels of IL-10. We later found that these CD19 CD27 plasmablasts significantly suppressed the mRNA and cytokine expression of IL-17A in PBMCs, as well as the expression of RAR-related orphan receptor gamma t (RORγt) in CD4 T cells. This suppressive effect did not involve the induction of Foxp3 regulatory T cells, since no upregulation of Foxp3 level was observed. Through IL-10/IL-10R blocking and exogenous IL-10 experiments, we found that these CD19 CD27 plasmablasts primarily mediated IL-17A suppression through IL-10 production. Other B cell-related mechanisms might also contribute to this inhibitory effect. In our cohort of patients, patients with high frequency of tumor-infiltrating IL-10 CD19 CD27 plasmablasts presented low IL-17A CD4 T cell frequency and better survival. Altogether, these results suggested that CD19 CD27 plasmablasts with Breg functions were associated with better prognosis in CRC, possibly by suppressing harmful Th17 inflammation.