Patching up the crypt: Innate immune cells orchestrate intestinal regeneration

Innate lymphoid cells (ILCs) are critical effectors of innate immunity and facilitate homeostasis as well as sustained adaptive immune responses, in particular to pathological infections. Recently, ILCs have emerged as novel orchestrators of tissue remodeling after injury, in the skin, thymus and intestine. In the intestine, group 3 innate lymphoid cells (ILC3s) and their IL-22 production are critical to maintain local crypt stem cells from T cell mediated killing in graft-versus-host (GVHD) disease, yet their mechanisms of action are not completely understood. Intestinal regeneration relies on the continuous replacement of the damaged epithelium by local stem cells, that are contained within a niche in the crypts of Lieberkühn. Interestingly, in mammals, hundreds of lymphoid clusters, namely cryptopatches and containing ILC3s, dendritic cells (DCs) and stromal cells, locate adjacent to the intestinal crypts. We hypothesized that cryptopatches play an important role in intestinal regeneration by conveying damage-associated signals to epithelial stem cell regulation. We set out to elucidate whether interactions between innate immune cells in cryptopatches and intestinal stem cells are significant to enhance mucosal healing, with the ultimate goal of improving epithelial barrier function in pathological conditions, such as alimentary mucositis and inflammatory bowel disease. This thesis untangles the importance of innate immune cells in driving epithelial responses to tissue damage and underscores the mechanisms by which ILC3s fine-tune stem cell responses to ensure epithelial regeneration, likely together with stromal cells and myeloid cells in cryptopatches

Yap1-Driven Intestinal Repair Is Controlled by Group 3 Innate Lymphoid Cells

Intestinal repair is driven by epithelial stem cells, but how these stem cells are instructed to initiate repair was unknown. Here, Romera-Hernández et al. report that epithelial proliferation after damage is independent of the stem cell-protective signal IL-22 but requires ILC3-dependent amplification of regenerative YAP1 signaling in stem cells.Tissue repair requires temporal control of progenitor cell proliferation and differentiation to replenish damaged cells. In response to acute insult, group 3 innate lymphoid cells (ILC3s) regulate intestinal stem cell maintenance and subsequent tissue repair. ILC3-derived IL-22 is important for stem cell protection, but the mechanisms of ILC3-driven tissue regeneration remain incompletely defined. Here we report that ILC3-driven epithelial proliferation and tissue regeneration are independent of IL-22. In contrast, ILC3s amplify the magnitude of Hippo-Yap1 signaling in intestinal crypt cells, ensuring adequate initiation of tissue repair and preventing excessive pathology. Mechanistically, ILC3-driven tissue repair is Stat3 indepe

Expression of Plet1 controls interstitial migration of murine small intestinal dendritic cells

Under homeostatic conditions, dendritic cells (DCs) continuously patrol the intestinal lamina propria. Upon antigen encounter, DCs ini

Interleukin-22 promotes intestinal-stem-cell-mediated epithelial regeneration

Epithelial regeneration is critical for barrier maintenance and organ function after intestinal injury. The intestinal stem cell (ISC) niche provides Wnt, Notch and epidermal growth factor (EGF) signals supporting Lgr5 + crypt base columnar ISCs for normal epithelial maintenance. However, little is known about the regu

Espacios y destinos turísticos en tiempos de globalización y crisis

2 volúmenesXII Coloquio de Geografía del Turismo, Ocio y Recreación de la Asociación de Geógrafos Españoles. Colmenarejo (Madrid), del 17 al 19 de junio de 2010.Este libro ha sido editado con la colaboración económica del Ministerio de Ciencia e Innovación (ref. CS02010-10416-E)