Saturday, July 23, 2016

Group 3 innate lymphoid cells express RET and respond to glia-neuron network

Few days back journal Nature reported very interesting study from Portugal. In there, the authors showed that intestine glial cells (which are neuron-satellites expressing the glial fibrillary acidic protein (GFAP) signal local innate ILC3 cells via tyrosine kinase receptor RET.

First, they showed that ILC3 express RET that receives signals from glial-derived neurotrophic factor family ligands.

Second, mice lacking RET specifically in ILC3 cells, Rorgt-CreRet fl/fl (RetΔ), displayed marked reduction of IL-22, a cytokine involved in epithelial homeostasis.

Third, RetΔ mice showed heightened T cell-independent susceptibility to chemical [DSS]-induced colitis and to intestinal infection with the attaching and effacing bacteria Citrobacter rodentium.

Fourth, it showed that glial cells (RFP, red) are located in close proximity to ILC3 cells (GFP, green).

Fifth, mice lacking MyD88 specifically in glial cells, Gfap-CreMyd88Δ mice, also displayed heightened susceptibility to DSS colitis, indicating cross-talk between TLR signaling, glial-derived RET ligands and IL-22 produced by ILC3.

In summary, this study revealed existence of a complex network of neuro-glial-immune interactions that result in optimal defense against intestinal irritation. 

David Usharauli

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