| First Author | Papoutsopoulou S | Year | 2021 |
| Journal | Front Immunol | Volume | 12 |
| Pages | 690817 | PubMed ID | 34220850 |
| Mgi Jnum | J:313739 | Mgi Id | MGI:6752214 |
| Doi | 10.3389/fimmu.2021.690817 | Citation | Papoutsopoulou S, et al. (2021) Impact of Interleukin 10 Deficiency on Intestinal Epithelium Responses to Inflammatory Signals. Front Immunol 12:690817 |
| abstractText | Interleukin 10 (IL-10) is a pleiotropic, anti-inflammatory cytokine that has a major protective role in the intestine. Although its production by cells of the innate and adaptive immune system has been extensively studied, its intrinsic role in intestinal epithelial cells is poorly understood. In this study, we utilised both ATAC sequencing and RNA sequencing to define the transcriptional response of murine enteroids to tumour necrosis factor (TNF). We identified that the key early phase drivers of the transcriptional response to TNF within intestinal epithelium were NFkappaB transcription factor dependent. Using wild-type and Il10(-/-) enteroid cultures, we showed an intrinsic, intestinal epithelium specific effect of IL-10 deficiency on TNF-induced gene transcription, with significant downregulation of identified NFkappaB target genes Tnf, Ccl20, and Cxcl10, and delayed overexpression of NFkappaB inhibitor encoding genes, Nfkbia and Tnfaip3. IL-10 deficiency, or immunoblockade of IL-10 receptor, impacted on TNF-induced endogenous NFkappaB activity and downstream NFkappaB target gene transcription. Intestinal epithelium-derived IL-10 appears to play a crucial role as a positive regulator of the canonical NFkappaB pathway, contributing to maintenance of intestinal homeostasis. This is particularly important in the context of an inflammatory environment and highlights the potential for future tissue-targeted IL-10 therapeutic intervention. |
