THE PRODUCTION OF ENDOGENOUS IL-10 BY PANETH CELLS AND ITS ROLE IN ENTEROID DEVELOPMENT

Abstract

The epithelium plays key roles in maintaining immune tolerance towards the microbiota while facilitating luminal inspection and defense. The epithelium is arguably an important player of gut immune defense, given that it can secrete a wide range of anti-microbial products, cytokines, and chemokines. In this study, we investigate the production and the role of IL-10, a potent anti-inflammatory cytokine, in intestinal epithelial cells. IL-10 has been established to be a key player of the intestinal innate immune system, and plays critical roles in gut homeostasis. Interest in intestinal IL-10 has mainly focused on how leukocyte-derived IL-10 influences the activity of other leukocytes, which consequently affect the state of the epithelium. Yet emerging evidence has claimed that the IL-10 receptors, as well as IL-10, are both detectable in the epithelium. Nevertheless, there are still knowledge gaps regarding the specific cell source and the role of IL-10 in the epithelium. Using multiple means of detection, Paneth cells within murine enteroids are shown to produce IL-10 and possess the IL-10 receptor. Additionally, other cells also possess the IL-10 receptor. The evidence from this study speaks to the likelihood of autocrine activity of IL-10 in Paneth cells and its impacts on the development of Paneth cell. Moreover, characterization of STAT3 activation through the IL-10 receptor revealed differential epithelial responses when stimulated from the apical versus basal membranes. Evidently, epithelial IL-10 might play a role in the regulation of STAT3 signaling through apical IL-10 receptor in intestinal epithelial cells. This study draws attention to intestinal epithelial cell as an unconventional contributor to the pool of mucosal IL-10. Importantly, the study further highlights the pleiotropism of IL-10, the effect of which greatly depends on the source, the target, and, for polarized cells such as intestinal epithelial cell, the polarity of exposure.