About this Research Topic
For a long time, the intestinal epithelial cells (IECs) were well known for their role as the boundary between the external environment and the intestinal tract. In the last decade, we have developed a better understanding of the role of IECs in generating, shaping and regulating the gut immune responses. Apart from being physical barrier, IECs play a pivotal role in sensing and directing the immune responses in order to maintain homeostasis. The cross-talk between the IECs and the immune system plays a critical role in regulating intestinal innate and adaptive immune responses. IECs include enterocytes, Paneth cells (PC), goblet cells (GC) and entero-endocrine cells, each of which can produce bioactive molecules with a broad array of functions including barrier formation, anti-microbial activity, and regulation of innate and adaptive immunity. Whilst IECs express toll-like receptors capable of responding to microbial products and activating NFκB, IEC mediated NFκB signalling is not necessarily pro-inflammatory. In fact, conditional knockout mice for IKKβ and NEMO show that loss of some elements of NFκB signalling in IEC results in aberrant immune responses and colitis. IEC produce many conditioning factors responsible for maintaining a balanced immune response. For example, thymic stromal lymphopoietin (TSLP), prostaglandin E2 (PGE2), transforming growth factor β (TGF β), interleukin-10 (IL-10), a proliferation-inducing ligand (APRIL) and B cell activating factor belonging to the TNF family (BAFF) from IECs are pivotal in maintaining a controlled response in the intestine by instructing the dendritic cells (DC) towards a non-inflammatory response. TSLP, PGE2 and IL-10 act on immature DC and macrophages in the lamina propria to drive restricted pro-inflammatory responses to the commensal microbes and generate either TH2, TH3 or Tr1 type of regulated non-inflammatory responses. The proximity of DC to IECs is likely to be critical for IEC mediated immune regulation and when epithelial cells are stressed by pathogens or other environmental factors it is likely that the production of the regulatory molecules is altered allowing appropriate DC activation to mount TH1, TH2 or TH17 responses. In addition to active participation in immune homeostasis, IECs talk to the external environment constantly to sample antigens for appropriate immune responses directed according to the type of material encountered. IECs play integral role in response to infections as well. Multiple mechanisms employed by IECs have been described in response to bacterial, viral and fungal infections. IEC mediated response to parasitic infection such as infection with Trichuris is another area of intense research due to its therapeutic potential for bowel diseases. Recently, research into the role of endoplasmic reticulum stress and oxidative stress in the pathogenesis of inflammatory bowel diseases indicate a central role for IECs, especially goblet cells and Paneth cells. A number of manuscripts in this series will address these multifaceted roles of intestinal epithelial cells and shed light on the new central paradigm that IECs shape intestinal immune responses.
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