IFN-γ plays an important role in innate and adaptive immunity. IFN-γ signaling is also involved in tumorigenesis, with both pro- and antitumor activities documented. We here report the characterization of intestinal tumorigenesis in ApcMin/+ mice that lack IFN-γ receptor. We observed that Ifngr1−/−ApcMin/+ mice are shorter-lived than Ifngr1+/+ApcMin/+ mice. The tumors in Ifngr1−/−ApcMin/+ mice are more likely to progress into invasive adenocarcinomas. Gene expression profiling by RNA sequencing revealed a significant upregulation of genes involved in inflammation and tissue remodeling in tumors of Ifngr1−/−ApcMin/+ mice when compared to those in Ifngr1+/+ApcMin/+ mice. In particular, five genes encoding matrix metallopeptidases (MMPs) were among the upregulated. On the other hand, genes that promote or maintain intestinal differentiation, such as Cdx2, Cdhr2 and Cdhr5, were downregulated. Tumor-associated macrophages were more abundant and were more favored toward M2 polarization in Ifngr1−/−ApcMin/+ mice than in Ifngr1+/+ApcMin/+ mice. Furthermore, the Ifngr1 was significantly downregulated in intestinal tumors when compared to mucosa. A similar trend was noted for human colorectal carcinomas. Together, our results indicate that adequate IFN-γ signaling is critical for maintaining a tumor-prohibitive microenvironment.
There are a large number of pathogens in the water where fish live, and the mucosal-associated lymphoid tissues (MALTs), such as skin, gill and intestine, are the first contact parts when pathogens infect fish. The secreted mucus of these tissues constitutes the first barrier for fish against the invasion of external pathogens. Mucosal immunity can identify and neutralize pathogens and induces immunocytes to devour pathogens and the like. As a key factor in the mucosal immune system, the polymeric immunoglobulin receptor (pIgR) is capable of mediating the transport and secretion of polymeric immunoglobulins towards mucus. The effective secretion of the pIgR is necessary for polymeric immunoglobulins (pIg) to exert mucosal defence and plays a significant role in fish immunity. With the deepening of research into fish immunoglobulins, the pIgR has become a research hotspot. The molecular structure, genetic structure and expression pattern of the pIgR and the important role it plays in mucosal immunity were summarized in this study, which contributed to a deeper understanding of fish mucosal immunity and laid a foundation for further exploration of the action mechanism and functions of the pIgR in fish.Produced by the AquacultureHub non-profit Foundation the IJA is an open-access, scientific journal, published on http://www.aquaculturehub.org/ To read papers free of charge, please register online at the above website. Sale of IJA papers is strictly forbidden.
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