Feedback mechanisms between M2 macrophages and Th17 cells in colorectal cancer patients.
IL-17 and IL-22 are linked to the development of intestinal inflammation and colorectal cancer (CRC). However, the maintenance of IL-17 and IL-22 production, as well as the cell type (Th17) that mediates these cytokines in CRC patients, remains unknown. To examine this, untreated CRC patients and healthy controls were recruited in this study. We first observed that CRC patients contained significantly elevated levels of IL-17- and IL-22-producing CD4+ T cells. The vast majority of IL-22-expressing CD4+ T cells also expressed IL-17. We then found that the production of both IL-17 and IL-22 required support from autologous monocytes, since the depletion of monocytes significantly downregulated IL-17 and IL-22 secretion. Naive T cells from CRC patients did not secrete IL-17 or IL-22 initially, but long-term coculture with autologous monocytes significantly upregulated IL-17 and IL-22 production in an IL-6-dependent manner. Blockade of IL-6 significantly reduced the levels of both IL-17 and IL-22. We then observed that CD163+ M2 macrophages were the main contributor of IL-6. Interestingly, incubation of monocytes with CCR4+CCR6+ Th17 cells resulted in significantly higher levels of CD163+ macrophages as well as higher IL-6 secretion, than incubation with non-Th17 CD4+ T cells. Together, our study discovered a positive feedback mechanism between Th17 and M2 macrophages in CRC patients.
['Mao|Hui|H|', 'Pan|Fei|F|', 'Guo|Hongxia|H|', 'Bu|Fangfang|F|', 'Xin|Tong|T|', 'Chen|Shukun|S|', 'Guo|Yajun|Y|']
D000368:Aged D015703:Antigens, CD D015214:Antigens, Differentiation, Myelomonocytic D015496:CD4-Positive T-Lymphocytes D002478:Cells, Cultured D018920:Coculture Techniques D015179:Colorectal Neoplasms D025461:Feedback, Physiological D005260:Female D005434:Flow Cytometry D006801:Humans D020381:Interleukin-17 D015850:Interleukin-6 D007378:Interleukins D008264:Macrophages D008297:Male D008875:Middle Aged D009000:Monocytes D054398:Receptors, CCR4 D054399:Receptors, CCR6 D011956:Receptors, Cell Surface D058504:Th17 Cells
Macrophages Th17 cells Colorectal cancer