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Publication : Dendritic cell derived IL-2 inhibits survival of terminally mature cells via an autocrine signaling pathway.

First Author  Balachander A Year  2015
Journal  Eur J Immunol Volume  45
Issue  5 Pages  1494-9
PubMed ID  25652593 Mgi Jnum  J:229640
Mgi Id  MGI:5752713 Doi  10.1002/eji.201445050
Citation  Balachander A, et al. (2015) Dendritic cell derived IL-2 inhibits survival of terminally mature cells via an autocrine signaling pathway. Eur J Immunol 45(5):1494-9
abstractText  DCs are crucial for sensing pathogens and triggering immune response. Upon activation by pathogen-associated molecular pattern (PAMP) ligands, GM-CSF myeloid DCs (GM-DCs) secrete several cytokines, including IL-2. DC IL-2 has been shown to be important for innate and adaptive immune responses; however, IL-2 importance in DC physiology has never been demonstrated. Here, we show that autocrine IL-2 signaling is functional in murine GM-DCs in an early time window after PAMPs stimulation. IL-2 signaling selectively activates the JAK/STAT5 pathway by assembling holo-receptor complexes at the cell surface. Using the sensitivity of targeted mass spectrometry, we show conclusively that GM-DCs express CD122, the IL-2 receptor beta-chain, at steady state. In myeloid DCs, this cytokine pathway inhibits survival of PAMP-matured GM-DCs which is crucial for maintaining immune tolerance and preventing autoimmunity. Our findings suggest that immune regulation by this novel autocrine signaling pathway can potentially be used in DC immunotherapy.
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