The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Interleukin-22 promotes intestinal-stem-cell-mediated epithelial regeneration
Open accessAbstract
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 regulation of the ISC compartment after tissue damage. Using ex vivo organoid cultures, here we show that innate lymphoid cells (ILCs), potent producers of interleukin-22 (IL-22) after intestinal injury, increase the growth of mouse small intestine organoids in an IL-22-dependent fashion. Recombinant IL-22 directly targeted ISCs, augmenting the growth of both mouse and human intestinal organoids, increasing proliferation and promoting ISC expansion. IL-22 induced STAT3 phosphorylation in Lgr5+ ISCs, and STAT3 was crucial for both organoid formation and IL-22-mediated regeneration. Treatment with IL-22 in vivo after mouse allogeneic bone marrow transplantation enhanced the recovery of ISCs, increased epithelial regeneration and reduced intestinal pathology and mortality from graft-versus-host disease. ATOH1-deficient organoid culture demonstrated that IL-22 induced epithelial regeneration independently of the Paneth cell niche. Our findings reveal a fundamental mechanism by which the immune system is able to support the intestinal epithelium, activating ISCs to promote regeneration.
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Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625
Mootha, V. K., Lindgren, C. M., Eriksson, K.-F., Subramanian, A., Sihag, S., Lehar, J., Puigserver, P., Carlsson, E., Ridderstråle, M., Laurila, E., et al. (2003) · Nature Genetics · doi:10.1038/ng1180 · Cited by 10,197
Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche
Sato, T., Vries, R. G., Snippert, H. J., van de Wetering, M., Barker, N., Stange, D. E., van Es, J. H., Abo, A., Kujala, P., Peters, P. J., et al. (2009) · Nature · doi:10.1038/nature07935 · Cited by 7,204
Identification of stem cells in small intestine and colon by marker gene Lgr5
Barker, N., van Es, J. H., Kuipers, J., Kujala, P., van den Born, M., Cozijnsen, M., Haegebarth, A., Korving, J., Begthel, H., Peters, P. J., et al. (2007) · Nature · doi:10.1038/nature06196 · Cited by 5,687
Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts
Sato, T., van Es, J. H., Snippert, H. J., Stange, D. E., Vries, R. G., van den Born, M., Barker, N., Shroyer, N. F., van de Wetering, M., & Clevers, H. (2011) · Nature · doi:10.1038/nature09637 · Cited by 2,510
STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing
Pickert, G., Neufert, C., Leppkes, M., Zheng, Y., Wittkopf, N., Warntjen, M., Lehr, H.-A., Hirth, S., Weigmann, B., Wirtz, S., et al. (2009) · Journal of Experimental Medicine · doi:10.1084/jem.20082683 · Cited by 1,043
Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation
Jenq, R. R., Ubeda, C., Taur, Y., Menezes, C. C., Khanin, R., Dudakov, J. A., Liu, C., West, M. L., Singer, N. V., Equinda, M. J., et al. (2012) · Journal of Experimental Medicine · doi:10.1084/jem.20112408 · Cited by 626
Self-citationLgr5 stem cells are indispensable for radiation-induced intestinal regeneration
Metcalfe, C., Kljavin, N. M., Ybarra, R., & de Sauvage, F. J. (2014) · Cell Stem Cell · doi:10.1016/j.stem.2013.11.008 · Cited by 575
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Defining trained immunity and its role in health and disease
Netea, M. G., Domínguez-Andrés, J., Barreiro, L. B., Chavakis, T., Divangahi, M., Fuchs, E., Joosten, L. A. B., van der Meer, J. W. M., Mhlanga, M. M., Mulder, W. J. M., et al. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-020-0285-6 · Cited by 2,690
The resilience of the intestinal microbiota influences health and disease
Sommer, F., Anderson, J. M., Bharti, R., Raes, J., & Rosenstiel, P. (2017) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2017.58 · Cited by 1,058
Engineering Stem Cell Organoids
Yin, X., Mead, B. E., Safaee, H., Langer, R., Karp, J. M., & Levy, O. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2015.12.005 · Cited by 866
Martini, E., Krug, S. M., Siegmund, B., Neurath, M. F., & Becker, C. (2017) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2017.03.007 · Cited by 668
Metadata
- Authors
- Lindemans, C. A., Calafiore, M., Mertelsmann, A. M., O’Connor, M. H., Dudakov, J. A., Jenq, R. R., Velardi, E., Young, L. F., Smith, O. M., Lawrence, G., Ivanov, J. A., Fu, Y.-Y., Takashima, S., Hua, G., Martin, M. L., O’Rourke, K. P., Lo, Y.-H., Mokry, M., Romera-Hernandez, M., Cupedo, T., Dow, L. E., Nieuwenhuis, E. E., Shroyer, N. F., Liu, C., Kolesnick, R., van den Brink, M. R. M., & Hanash, A. M.
- Venue
- Nature
- Published
- 2015-12
- Volume
- 528
- Issue
- 7583
- Pages
- 560-564
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2195777839
- Cited by
- 1,109
- References
- 8
- FWCI
- 33.53
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Interleukin-22 promotes intestinal-stem-cell-mediated epithelial regeneration. https://app.cochat.ai/papers/10.1038/nature16460
- The paper
- Lindemans, C. A., Calafiore, M., Mertelsmann, A. M., O’Connor, M. H., Dudakov, J. A., Jenq, R. R., Velardi, E., Young, L. F., Smith, O. M., Lawrence, G., Ivanov, J. A., Fu, Y.-Y., Takashima, S., Hua, G., Martin, M. L., O’Rourke, K. P., Lo, Y.-H., Mokry, M., Romera-Hernandez, M., . . . Hanash, A. M. (2015). Interleukin-22 promotes intestinal-stem-cell-mediated epithelial regeneration. Nature. https://doi.org/10.1038/nature16460
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
