Retour sur le 14ème Symposium International « DC 2016 », Shanghai, Chine par Carla Lippens, lauréate d’une bourse de voyage CFCD.
The 14th International Symposium on Dendritic cells was organised this autumn by Pr. Xuetao and his team, who warmly welcomed us at the International Convention Center in the amazing city of Shanghai. Focused on DCs, the scientific program of the congress was amazing, and covered a broad panel of topics, from DC ontogeny and development to DC involvement in diseases, and their use as therapeutic products in autoimmunity and cancers. Pleinary and short talks sessions, as well as keynote lectures, largely updated last findings on DCs and shared the forefront innovating technics used to deeply and even more accurately study these important cells that DCs are. Here follows a brief summary of some of them.
C. L. Scott, from Bart Lambrecht’s lab, presented her paper published this year, showing that the transcription (TF) factor zinc finger E box-binding homeobox 2 (Zeb2) regulates the development of both conventional and plasmacytoid DCs. Using mice conditionally lacking Zeb2 expression or overexpressing Zeb2 in CD11c+ cells, they reported that Zeb2 regulates commitment to both the cDC2 and pDC lineages through the repression of Id2. Then, in reference to another paper published early september this year, she exposed their last findings about the TF Interferon regulatory factor-8 (IRF8). More specifically, she insisted on the fact that IRF8 is critical for the control of pDC activation but not for pDC development, as it is commonly accepted.
Pr. C. Reis e Sousa gave us an overview of their finding on DC seeding in different types of tissues. Few years ago they first demonstrated that DNGR-1 (CLEC-9a) can be considered as a DC lineage marker, starting to be expressed by CD115+ common dendritic precursors. In Shanghai 2016 meeting, he exposed how they are doing fate mapping of single DC precursors by using Clec9a-Cre crossed with ROSA-confetti mice, that harbor a Brainbow-2.1 construct encoding nGFP, YFP, RFP, and mCFP flanked by loxPs in the ROSA26 locus. By performing microscopic analysis they found that in small intestine, DCs coming from 1 colour pre-DC precursor seem to be clustered. They are currently analysing the presence of different DC subsets based on surface markers as CD11b, CD64 and CD103 to identify whether or not 1 pre-DC precursor can give rise to 1 or several DC subsets.
Pr. J. Villadangos and his group are studying the impact of direct (through PAMP sensing) versus indirect (cytokines) activation on DCs. By transcriptomic analysis they show that splenic WT versus TLR9-/- DCs isolated from WT+TLR9WT chimeric mice injected with CpG exhibit different gene expression profiles, thus suggesting diverse outcomes for DCs when they are directly (WT DCs) or indirectly (TLR9-/- DCs) activated. Furthermore, using different models of systemic infections mimicking system inflammation response syndrome (SIRS), they described that following activation DCs are rapidly replaced by immature, poorly phagocytic DCs exhibiting impaired ability to present and cross-present antigens. They qualified these cells as “paralysed DCs”, and demonstrated using conditional KO mice that DC paralysis is induced by TGF-β and GM-CSF.
Following the observation that insulin resistance correlates with IFN-I response in human obese visceral adipose tissues (VATs), Pr. D. Ganguly showed that plasmacytoid dendritic cells (pDCs) are specifically recruited in obese VATs through CMKLR1/Chermerin axis. Using in vitro assays they demonstrated that IFN-I production by TLR9-activated pDCs leads to the pro-inflammatory polarization of M2 to M1 adipose-resident macrophages which contribute to insulin resistance.
S. Caielli, who is working with Dr. Virginia Pascual and in collaboration with J. Banchereau, presented her last paper published this year in JEM relating the exceptional ability of oxidizied mitochondrial DNA (ox mtDNA) to activate IFN-I production by pDCs. They reported that anti-Sm/ribonucleotide protein (RNP) antibodies in addition to IFN-α induce the release of ox mtDNA by neutrophils in SLE patients. They showed that SLE neutrophil-extruded ox mtDNA is highly interferogenic. Furthermore they demonstrated that ox mtDNA-activated pDCs induce unique CD4+ T cells which are not anergic and that express high level of IFNγ and IL-10.
Finally, I particularly appreciated the talk of Pr. G. Kroemer about the contribution of autophagy in anti-tumoral immune responses. He and his team elegantly demonstrate that autophagy of tumoral cells, either induced by fasting or through the use of caloric restriction mimetics, significantly enhanced chemotherapy effects, a phenomenon which is lost in mice with Atg5KO tumors. They report that autophagy of cancer cells promotes ATP release that contributes to the attraction of DCs into the tumor through the ATP/P2Rγ axis, and subsequently improves antitumoral responses.
To finish, I would like to thanks the CFCD for giving me the opportunity to attend this great meeting, to present my work and to discuss my results with DC experts.
The 14th International Symposium on Dendritic cells was organised this autumn by Pr. Xuetao and his team, who warmly welcomed us at the International Convention Center in the amazing city of Shanghai. Focused on DCs, the scientific program of the congress was amazing, and covered a broad panel of topics, from DC ontogeny and development to DC involvement in diseases, and their use as therapeutic products in autoimmunity and cancers. Pleinary and short talks sessions, as well as keynote lectures, largely updated last findings on DCs and shared the forefront innovating technics used to deeply and even more accurately study these important cells that DCs are. Here follows a brief summary of some of them.
C. L. Scott, from Bart Lambrecht’s lab, presented her paper published this year, showing that the transcription (TF) factor zinc finger E box-binding homeobox 2 (Zeb2) regulates the development of both conventional and plasmacytoid DCs. Using mice conditionally lacking Zeb2 expression or overexpressing Zeb2 in CD11c+ cells, they reported that Zeb2 regulates commitment to both the cDC2 and pDC lineages through the repression of Id2. Then, in reference to another paper published early september this year, she exposed their last findings about the TF Interferon regulatory factor-8 (IRF8). More specifically, she insisted on the fact that IRF8 is critical for the control of pDC activation but not for pDC development, as it is commonly accepted.
Pr. C. Reis e Sousa gave us an overview of their finding on DC seeding in different types of tissues. Few years ago they first demonstrated that DNGR-1 (CLEC-9a) can be considered as a DC lineage marker, starting to be expressed by CD115+ common dendritic precursors. In Shanghai 2016 meeting, he exposed how they are doing fate mapping of single DC precursors by using Clec9a-Cre crossed with ROSA-confetti mice, that harbor a Brainbow-2.1 construct encoding nGFP, YFP, RFP, and mCFP flanked by loxPs in the ROSA26 locus. By performing microscopic analysis they found that in small intestine, DCs coming from 1 colour pre-DC precursor seem to be clustered. They are currently analysing the presence of different DC subsets based on surface markers as CD11b, CD64 and CD103 to identify whether or not 1 pre-DC precursor can give rise to 1 or several DC subsets.
Pr. J. Villadangos and his group are studying the impact of direct (through PAMP sensing) versus indirect (cytokines) activation on DCs. By transcriptomic analysis they show that splenic WT versus TLR9-/- DCs isolated from WT+TLR9WT chimeric mice injected with CpG exhibit different gene expression profiles, thus suggesting diverse outcomes for DCs when they are directly (WT DCs) or indirectly (TLR9-/- DCs) activated. Furthermore, using different models of systemic infections mimicking system inflammation response syndrome (SIRS), they described that following activation DCs are rapidly replaced by immature, poorly phagocytic DCs exhibiting impaired ability to present and cross-present antigens. They qualified these cells as “paralysed DCs”, and demonstrated using conditional KO mice that DC paralysis is induced by TGF-β and GM-CSF.
Following the observation that insulin resistance correlates with IFN-I response in human obese visceral adipose tissues (VATs), Pr. D. Ganguly showed that plasmacytoid dendritic cells (pDCs) are specifically recruited in obese VATs through CMKLR1/Chermerin axis. Using in vitro assays they demonstrated that IFN-I production by TLR9-activated pDCs leads to the pro-inflammatory polarization of M2 to M1 adipose-resident macrophages which contribute to insulin resistance.
S. Caielli, who is working with Dr. Virginia Pascual and in collaboration with J. Banchereau, presented her last paper published this year in JEM relating the exceptional ability of oxidizied mitochondrial DNA (ox mtDNA) to activate IFN-I production by pDCs. They reported that anti-Sm/ribonucleotide protein (RNP) antibodies in addition to IFN-α induce the release of ox mtDNA by neutrophils in SLE patients. They showed that SLE neutrophil-extruded ox mtDNA is highly interferogenic. Furthermore they demonstrated that ox mtDNA-activated pDCs induce unique CD4+ T cells which are not anergic and that express high level of IFNγ and IL-10.
Finally, I particularly appreciated the talk of Pr. G. Kroemer about the contribution of autophagy in anti-tumoral immune responses. He and his team elegantly demonstrate that autophagy of tumoral cells, either induced by fasting or through the use of caloric restriction mimetics, significantly enhanced chemotherapy effects, a phenomenon which is lost in mice with Atg5KO tumors. They report that autophagy of cancer cells promotes ATP release that contributes to the attraction of DCs into the tumor through the ATP/P2Rγ axis, and subsequently improves antitumoral responses.
To finish, I would like to thanks the CFCD for giving me the opportunity to attend this great meeting, to present my work and to discuss my results with DC experts.