title: Dendritic cell derived IL-2 inhibits survival of terminally mature cells via an autocrine signaling pathway.
abstract: 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 β-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.
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
authors: Akhila
authors: A
authors: Balachander
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
authors: Sabrina
authors: S
authors: Nabti
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
authors: Radoslaw M
authors: RM
authors: Sobota
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
authors: Shihui
authors: S
authors: Foo
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
authors: Francesca
authors: F
authors: Zolezzi
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
authors: Bernett T K
authors: BT
authors: Lee
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
authors: Michael
authors: M
authors: Poidinger
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
authors: Paola
authors: P
authors: Ricciardi-Castagnoli
mesh_terms: D000818:Animals; D019898:Autocrine Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D007376:Interleukin-2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D053646:Interleukin-2 Receptor beta Subunit / Q000235:genetics / Q000378:metabolism; D053612:Janus Kinases / Q000378:metabolism; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D021122:Protein Subunits; D015375:Receptors, Interleukin-2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051192:Receptors, Pattern Recognition / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D047071:beta-Glucans / Q000494:pharmacology
chemical_list: C508022:Il2rb protein, mouse; D007376:Interleukin-2; D053646:Interleukin-2 Receptor beta Subunit; D008024:Ligands; D021122:Protein Subunits; D015375:Receptors, Interleukin-2; D051192:Receptors, Pattern Recognition; D050799:STAT5 Transcription Factor; D047071:beta-Glucans; C038459:curdlan; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D053612:Janus Kinases
keywords: Autocrine signaling; DCs; IL-2; Immune regulation; STAT5