RT Journal Article
T1 Glial-cell-derived neuroregulators control type 3 innate lymphoid cells and gut defence
A1 Ibiza Martinez, Sales
A1 García Cassani, Bethania
A1 Ribeiro, Hélder
A1 Carvalho, Tânia
A1 Almeida, Luís
A1 Marques, Rute
A1 Misic, Ana M.
A1 Bartow McKenney, Casey
A1 Larson, Denise M.
A1 Pavan, William J.
A1 Eberl, Gérard
A1 Grice, Elizabeth A.
A1 Veiga Fernandes, Henrique
AB Group 3 innate lymphoid cells (ILC3) are major regulators of inflammation and infection at mucosal barriers1. ILC3 development is thought to be programmed1, but how ILC3 perceive, integrate and respond to local environmental signals remains unclear. Here we show that ILC3 in mice sense their environment and control gut defence as part of a glial–ILC3–epithelial cell unit orchestrated by neurotrophic factors. We found that enteric ILC3 express the neuroregulatory receptor RET. ILC3-autonomous Ret ablation led to decreased innate interleukin-22 (IL-22), impaired epithelial reactivity, dysbiosis and increased susceptibility to bowel inflammation and infection. Neurotrophic factors directly controlled innate Il22 downstream of the p38 MAPK/ERK-AKT cascade and STAT3 activation. Notably, ILC3 were adjacent to neurotrophic-factor-expressing glial cells that exhibited stellate-shaped projections into ILC3 aggregates. Glial cells sensed microenvironmental cues in a MYD88-dependent manner to control neurotrophic factors and innate IL-22. Accordingly, glial-intrinsic Myd88 deletion led to impaired production of ILC3-derived IL-22 and a pronounced propensity towards gut inflammation and infection. Our work sheds light on a novel multi-tissue defence unit, revealing that glial cells are central hubs of neuron and innate immune regulation by neurotrophic factor signals.
PB Springer Nature
SN 0028-0836
YR 2016
FD 2016-07-13
LK https://hdl.handle.net/20.500.14352/115966
UL https://hdl.handle.net/20.500.14352/115966
LA eng
NO Ibiza S*, García-Cassani B*, Ribeiro H, Carvalho T, Almeida L, Marques R, et al. Glial-cell-derived neuroregulators control type 3 innate lymphoid cells and gut defence. Nature. 2016 Jul 13;535(7612):440–3
DS Docta Complutense
RD 9 abr 2025