The encephalitogenicity of TH17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF

By Mohamed El-behi, B. Ciric, Hong Dai, Yaping Yan, M. Cullimore, F. Safavi, Guang-Xian Zhang, B. Dittel, A. Rostami. Nature Immunology, 2011

1,073 citations recorded by the source corpus.

Interleukin 17 (IL-17)-producing helper T cells (TH17 cells) require exposure to IL-23 to become encephalitogenic, but the mechanism by which IL-23 promotes their pathogenicity is not known. Here we found that IL-23 induced production of the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) in TH17 cells and that GM-CSF had an essential role in their encephalitogenicity. Our findings identify a chief mechanism that underlies the important role of IL-23 in autoimmune diseases. IL-23 induced a positive feedback loop whereby GM-CSF secreted by TH17 cells stimulated the production of IL-23 by antigen-presenting cells. Such cross-regulation of IL-23 and GM-CSF explains the similar pattern of resistance to autoimmunity when either of the two cytokines is absent and identifies TH17 cells as a crucial source of GM-CSF in autoimmune inflammation.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/836c5d9b1f6cce4ad4bd90bd5af0dcaddf0966b1

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. Y. Belkaid
2. Miriam Merad
3. D. Hashimoto
4. P. Italiani
5. M. Bogunovic
6. D. Boraschi
7. A. Mortha
8. O. Harrison

Citations in the corpus

• Microbiota-Dependent Crosstalk Between Macrophages and ILC3 Promotes Intestinal Homeostasis (2014, positive): “RORgt T helper 17 (TH17) cells can produce large amounts of Csf2 in the inflamed brain and intestine (26, 27, 32).”
• From Monocytes to M1/M2 Macrophages: Phenotypical vs. Functional Differentiation (2014, background): “GM-CSF can support monocyte expansion and differentiation in vitro (25, 114), and it seems to be mainly involved in induction of hematopoiesis during inflammation rather than in homeostasis (115, 116).”
• The Microbiome in Infectious Disease and Inflammation (2012, neutral): “The production of granulocytemacrophage colony-stimulating factor (GMCSF) is one of the mechanisms by which Th17 cells mediate their effector functions (143).”