19:10 - 21:00
Room: Ishikawa Ongakudō Interchange Hall
Poster Session
The quantity of initial FcRγ signaling determines cytokine profile in dendritic cells
Miyuki Watanabe1, 2, Sho Yamasaki1, 2
1Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Japan, 2Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan

We previously demonstrated that C-type lectin receptors Mincle and Dectin-2 can induce inflammatory cytokines in dendritic cells (DCs) by recognizing mycobacterial components, such as trehalose-6,6’-dimycolate (TDM) and mannose-capped lipoarabinomannan (Man-LAM), respectively. In contrast, only Dectin-2, not Mincle, induces large amount of IL-2 production in DCs. IL-2 derived from DCs is known to promote T cell priming. However, it is unknown why different receptors can induce distinct responses, despite they share the same FcRγ chain as a signaling subunit. Dectin-2 is constitutively expressed in resting myeloid cells, while Mincle expression is induced in response to several inflammatory stimuli. We therefore asked whether “expression pattern” or “structural feature” was required for IL-2 production. To this end, we generated transgenic (Tg) mice constitutively expressing Mincle or Mincle-Dectin-2 chimeric receptor, which replaced the intracellular domain of Mincle with the corresponding domain of Dectin-2 (MincleDM). Upon Mincle ligand TDM stimulation, BMDCs from MincleDM Tg mice produced significant amount of IL-2, in sharp contrast to WT BMDCs. TNF production was similarly observed in BMDCs regardless of the transgenes. We next compared the IL-2 production in BMDCs from several Tg lines being different levels of MincleDM and found that a certain threshold level of receptor expression is required for IL-2 production by TDM. Intriguingly, TDM induced the production of IL-2 in Mincle Tg BMDCs that constitutively express WT Mincle. These results suggest that signal intensity in the early phase through the constitutive expression receptor, but not Dectin-2 structure, is a key factor to produce IL-2. Collectively, we propose that ITAM signal kinetics can determine cytokine profile in DCs.


Reference:
Tu-P4-30
Session:
Poster Session 4 “Regulation of cytokine production”
Presenter/s:
Miyuki Watanabe
Presentation type:
Poster Presentation
Room:
Ishikawa Ongakudō Interchange Hall
Date:
Tuesday, 31 October 2017
Time:
19:10 - 21:00
Session times:
19:10 - 21:00