@article{2da5bd30b20d49078175016208e4c545,
title = "Expanded ILC2s in human infant intestines promote tissue growth",
abstract = "Early life is characterized by extraordinary challenges, including rapid tissue growth and immune adaptation to foreign antigens after birth. During this developmental stage, infants have an increased risk of immune-mediated diseases. Here, we demonstrate that tissue-resident, interleukin (IL)-13- and IL-4-producing group 2 innate lymphoid cells (ILC2s) are enriched in human infant intestines compared to adult intestines. Organoid systems were employed to assess the role of infant intestinal ILC2s in intestinal development and showed that IL-13 and IL-4 increased epithelial cell proliferation and skewed cell differentiation toward secretory cells. IL-13 furthermore upregulated the production of mediators of type-2 immunity by infant intestinal epithelial cells, including vascular endothelial growth factor-A and IL-26, a chemoattractant for eosinophils. In line with these in vitro findings increased numbers of eosinophils were detected in vivo in infant intestines. Taken together, ILC2s are enriched in infant intestines and can support intestinal development while inducing an epithelial secretory response associated with type 2 immune-mediated diseases.",
author = "M{\"o}ller, {Kimberly J.} and Wegner, {Lucy H. M.} and Jakob Malsy and Baumdick, {Martin E.} and Malte Borggrewe and Ana Jordan-Paiz and Jung, {Johannes M.} and Gl{\`o}ria Martrus and Paul Kretschmer and Sagebiel, {Adrian F.} and Schreurs, {Ren{\'e}e R. C. E.} and Hagen, {Sven H.} and Gunter Burmester and Clauditz, {Till S.} and Pals, {Steven T.} and Michael Boettcher and Nathaniel Melling and Guido Sauter and Christian Tomuschat and Ingo K{\"o}nigs and Udo Schumacher and Marcus Altfeld and Bernink, {Jochem H.} and Daniel Perez and Konard Reinshagen and Bunders, {Madeleine J.}",
note = "Funding Information: This work was supported by a grant from DZIF, the Deutsche Forschungsgemeinschaft (DFG; SFB841), EFRE 2014-2020 REACT-EU and the Daisy Hu{\"e}t R{\"o}ell Foundation. Funding Information: The authors would like to thank all donors and their parents for participation in this study. Further we thank the colleagues from the Department of Pediatric Surgery, as well as Department of General, Visceral, and Thoracic Surgery of the UKE (Hamburg) for the collection of intestinal tissues; Cordula Gr{\"u}ttner for technical assistance with qPCR and Arne D{\"u}sedau and Jana Hennesen for technical assistance for flow cytometric analyses and Fluidigm experiments. S.H.H. is an employee at AdaptVac, a company commercializing virus-like particle display technology and vaccines. The Leibniz Institute of Virology is supported by the Free and Hanseatic City of Hamburg and the Federal Ministry of Health. The graphical abstract was created with BioRender.com . Publisher Copyright: {\textcopyright} 2023 The Author(s)",
year = "2023",
month = aug,
doi = "https://doi.org/10.1016/j.mucimm.2023.04.004",
language = "English",
volume = "16",
pages = "408--421",
journal = "Mucosal Immunology",
issn = "1933-0219",
publisher = "Nature Publishing Group",
number = "4",
}