Stromal Immunology Group: 2nd Annual Meeting
Möller Centre, University of Cambridge 6-7th November 2013 Organisers: Matt Lakins, Benjamin Owens and Patty Sachamitr Meeting Report: Emily Colbeck The one and a half day conference kicked off with the first session of talks on Wednesday afternoon, chaired by Mark Coles (University of York). First up was Brigitta Stockinger (NIMR, London), on the shaping of inflammatory immune responses by environmental stimuli. Professor Stockinger described distinguishing characteristics of pathogenic Th17 cells in autoimmunity, and intestinal Th17 cells that protect against microbial attack. The second part of the talk focused on the environmental sensor, aryl hydrocarbon receptor (AhR), which acts as an ‘inflammatory brake’ to prevent catastrophic autoimmune responses. Next up was Aris Economides (Regeneron Pharmaceuticals Inc, New York) who talked us through the development of the VelocImmune® discovery platform for production of human therapeutic antibodies in mice, and the pioneering of a new method for generation of conditional alleles, termed ‘COIN’ (Conditional by Inversion) technology. |
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After coffee, Burkhard Ludewig (St Gallen, Switzerland) showed us some beautiful optical projection tomography images during a fascinating talk on the role of mesenchymal and endothelial stromal organiser cells in lymphoid organs. Professor Ludewig presented novel data illustrating the requirement for direct triggering of the LymphotoxinβReceptor on vascular endothelium early in development for formation of functioning High Endothelial Venules (HEV) in lymph nodes. Rounding off the first afternoon of talks was Tom Cupedo (Erasmus MC, Netherlands) who spoke of Rorγt+ innate lymphoid cells (ILCs) at the intersection between innate and adaptive immunity, and the persistence of a marginal reticular cell (MRC) population into adulthood in both mouse and human. Everyone then enjoyed welcome drinks and a casual poster viewing session before dinner.
Following a warm welcome of coffee and mini French pastries, the second day of the conference began with the second session of talks, chaired by Matt Lakins (University of Cambridge) and Patty Sachamitr (University of Oxford). Paul-Peter Tak (AMC Amsterdam & GSK) opened with a stimulating talk on the role of pathogenic fibroblast-like synoviocytes (FLS) in local inflammation of rheumatoid arthritis (RA), and the different pathogenetic subsets of this syndrome. Professor Tak suggested new approaches of targeting epigenetic processes, already strongly implicated in RA development, specifically in the FLS population, to achieve better response rates in patients. Guillaume Desanti (University of Birmingham) then extended the theme of RA by telling us about the regulation of increased Gp38 (Podoplanin) expression on synovial fibroblasts in disease by inflammatory signals via CLEC-2 (Gp38 ligand) expression on leukocytes.
Next, Sophie Acton (CRUK LRI & University College London) then described a mechanism of lymph node expansion during acute inflammation, whereby CLEC-2+ dendritic cells signal via Gp38 on Follicular Reticular Cells (FRCs) to alter acto-myosin cytoskeletal dynamics, thereby facilitating lymph node ‘swelling’. The second session concluded with an exciting presentation from Cyrille Mionnet (University Marseille de Luminy) focusing on a novel population of stromal cells found in secondary lymphoid tissues; namely Versatile Stromal Cells (VSCs). Dr Mionnet explained that VSCs are distinct from FRCs, pre-FDCs and FDCs in terms of gene expression, where their role is the prevention of B cell ‘trespassing’ from swollen B cell follicles into T cell zones during inflammation. Attendees then had an hour and a half for poster browsing, bargain hunting at exhibitor’s stands and ‘talking stroma’ over a delicious lunch provided by the Møller Centre.
Following lunch, there were a series of short talks during session three, chaired by Ben Owens (University of Oxford) and Alice Denton (University of Cambridge). First of all, Bridget Glaysher (University of York) spoke of the development of in vitro engineered human lymphoid tissue. Stromal cells were pretreated with inflammatory cytokines which resulted in an upregulation of adhesion molecule expression, that subsequently lead to lymphocyte recruitment into an organised structure. Jasper Koning (VUMC, Amsterdam) then told us about a population of nestin-expressing mesenchymal cells that represent the precursors of FRC, FDC and MRC stromal cell lineages, and blood endothelial cells of HEV and lymphatic endothelial cells in the developing lymph node.
Next, Helen McGettrick (University of Birmingham) described interesting findings on the phenotype of synovial fibroblasts from different stages of arthritic disease. Dr McGettrick explained that synovial fibroblasts lost their immunosuppressive phenotype early in RA development, but that fibroblasts acquire an increased ability to recruit peripheral blood lymphocytes (PBL) in a disease severity-dependent manner. Rounding off the series of short talks was Donald Palmer (Royal Veterinary College, University of London) who described age associated changes in the stromal cell microenvironment of primary and secondary lymphoid tissues that may be responsible for the phenomenon of immunosenescence; a reduced ability to mount an effective immune response with advancing age. Lastly, qualifying for the prize of furthest-travelled speaker, was Scott Mueller (University of Melbourne, Australia), who presented some impressive imaging techniques his lab are using to dissect lymphoid stromal cell responses to viral infection. Specifically, Dr Mueller described the expansion of HEV, FRC and lymphatics in lymph nodes responsive to localised infections such as herpes simplex virus, and the differences in the response of splenic FRC to acute versus chronic infection in terms of gene expression.
Following a coffee break, the final series of talks, chaired by Sophie Acton (CRUK and LRI, London) and Jasper Koning (VUMC, Amsterdam), got started with a stimulating talk by Francesca Barone (University of Birmingham) on tertiary lymphoid organs (TLOs) that form during inflammatory disease. Dr Barone described the involvement of stromal cells in the dynamic phases of adenovirus infection in mice, including the activation of stromal cells by IL13 during the induction phase, and later stromal cell expansion via cytokines such as IL22. Olga Cordeiro (University of Strasbourg) then told the audience about her work on the elucidation of the role of RANK-RANKL signaling in lymph node development and homeostasis. In a transgenic mouse model in which RANK ligand is overexpressed, Dr Cordeiro and colleagues have found that lymphatic endothelial cells (LECs) demonstrate the greatest changes in gene expression and identified MadCAM-1 as an important downstream target of RANKL signaling.
Concluding the short talks of the conference was Lisa Spary (Cardiff University), who presented a study on the characterization of prostate cancer associated stroma and the influence of such cells on infiltration and function of immune cells. Dr Spary’s group has found that prostate cancer associated stroma attracts undifferentiated monocytes, which, once in the presence of tumour stroma, take on an immunosuppressive role, expressing factors such as the cytokine IL10. Finally, to conclude the conference, Doug Fearon (University of Cambridge), gave a fascinating talk on the failure of immunosurveillance in pancreatic ductal adenocarcinoma (PDA). Professor Fearon explained that the observed lack of response to anti-PD-L1 and anti-CTLA-4 antibody therapies in patients could be explained by the presence of Fibroblast Activation Protein α (FAPα) positive cancer associated fibroblasts (CAFs) in tumours. By illustrating the ability to arrest tumour growth in a T cell dependent manner following abrogation of FAP+ CAF mediated immunosuppression, Professor Fearon justified such an approach as a novel therapeutic proposal to target PDA. The final session of the meeting was rounded off with prize giving; congratulations to Lisa Spary and Chris Hansell for best short talk and best poster prize, respectively.
After a buzzing drinks reception, discussions continued over a delicious conference dinner at the University Arms Hotel. This provided further opportunity to network with renowned names in the field of stromal immunology, and to ‘talk stroma’. Congratulations to the organisers for putting on a highly stimulating conference; here’s to next year’s meeting!
Following a warm welcome of coffee and mini French pastries, the second day of the conference began with the second session of talks, chaired by Matt Lakins (University of Cambridge) and Patty Sachamitr (University of Oxford). Paul-Peter Tak (AMC Amsterdam & GSK) opened with a stimulating talk on the role of pathogenic fibroblast-like synoviocytes (FLS) in local inflammation of rheumatoid arthritis (RA), and the different pathogenetic subsets of this syndrome. Professor Tak suggested new approaches of targeting epigenetic processes, already strongly implicated in RA development, specifically in the FLS population, to achieve better response rates in patients. Guillaume Desanti (University of Birmingham) then extended the theme of RA by telling us about the regulation of increased Gp38 (Podoplanin) expression on synovial fibroblasts in disease by inflammatory signals via CLEC-2 (Gp38 ligand) expression on leukocytes.
Next, Sophie Acton (CRUK LRI & University College London) then described a mechanism of lymph node expansion during acute inflammation, whereby CLEC-2+ dendritic cells signal via Gp38 on Follicular Reticular Cells (FRCs) to alter acto-myosin cytoskeletal dynamics, thereby facilitating lymph node ‘swelling’. The second session concluded with an exciting presentation from Cyrille Mionnet (University Marseille de Luminy) focusing on a novel population of stromal cells found in secondary lymphoid tissues; namely Versatile Stromal Cells (VSCs). Dr Mionnet explained that VSCs are distinct from FRCs, pre-FDCs and FDCs in terms of gene expression, where their role is the prevention of B cell ‘trespassing’ from swollen B cell follicles into T cell zones during inflammation. Attendees then had an hour and a half for poster browsing, bargain hunting at exhibitor’s stands and ‘talking stroma’ over a delicious lunch provided by the Møller Centre.
Following lunch, there were a series of short talks during session three, chaired by Ben Owens (University of Oxford) and Alice Denton (University of Cambridge). First of all, Bridget Glaysher (University of York) spoke of the development of in vitro engineered human lymphoid tissue. Stromal cells were pretreated with inflammatory cytokines which resulted in an upregulation of adhesion molecule expression, that subsequently lead to lymphocyte recruitment into an organised structure. Jasper Koning (VUMC, Amsterdam) then told us about a population of nestin-expressing mesenchymal cells that represent the precursors of FRC, FDC and MRC stromal cell lineages, and blood endothelial cells of HEV and lymphatic endothelial cells in the developing lymph node.
Next, Helen McGettrick (University of Birmingham) described interesting findings on the phenotype of synovial fibroblasts from different stages of arthritic disease. Dr McGettrick explained that synovial fibroblasts lost their immunosuppressive phenotype early in RA development, but that fibroblasts acquire an increased ability to recruit peripheral blood lymphocytes (PBL) in a disease severity-dependent manner. Rounding off the series of short talks was Donald Palmer (Royal Veterinary College, University of London) who described age associated changes in the stromal cell microenvironment of primary and secondary lymphoid tissues that may be responsible for the phenomenon of immunosenescence; a reduced ability to mount an effective immune response with advancing age. Lastly, qualifying for the prize of furthest-travelled speaker, was Scott Mueller (University of Melbourne, Australia), who presented some impressive imaging techniques his lab are using to dissect lymphoid stromal cell responses to viral infection. Specifically, Dr Mueller described the expansion of HEV, FRC and lymphatics in lymph nodes responsive to localised infections such as herpes simplex virus, and the differences in the response of splenic FRC to acute versus chronic infection in terms of gene expression.
Following a coffee break, the final series of talks, chaired by Sophie Acton (CRUK and LRI, London) and Jasper Koning (VUMC, Amsterdam), got started with a stimulating talk by Francesca Barone (University of Birmingham) on tertiary lymphoid organs (TLOs) that form during inflammatory disease. Dr Barone described the involvement of stromal cells in the dynamic phases of adenovirus infection in mice, including the activation of stromal cells by IL13 during the induction phase, and later stromal cell expansion via cytokines such as IL22. Olga Cordeiro (University of Strasbourg) then told the audience about her work on the elucidation of the role of RANK-RANKL signaling in lymph node development and homeostasis. In a transgenic mouse model in which RANK ligand is overexpressed, Dr Cordeiro and colleagues have found that lymphatic endothelial cells (LECs) demonstrate the greatest changes in gene expression and identified MadCAM-1 as an important downstream target of RANKL signaling.
Concluding the short talks of the conference was Lisa Spary (Cardiff University), who presented a study on the characterization of prostate cancer associated stroma and the influence of such cells on infiltration and function of immune cells. Dr Spary’s group has found that prostate cancer associated stroma attracts undifferentiated monocytes, which, once in the presence of tumour stroma, take on an immunosuppressive role, expressing factors such as the cytokine IL10. Finally, to conclude the conference, Doug Fearon (University of Cambridge), gave a fascinating talk on the failure of immunosurveillance in pancreatic ductal adenocarcinoma (PDA). Professor Fearon explained that the observed lack of response to anti-PD-L1 and anti-CTLA-4 antibody therapies in patients could be explained by the presence of Fibroblast Activation Protein α (FAPα) positive cancer associated fibroblasts (CAFs) in tumours. By illustrating the ability to arrest tumour growth in a T cell dependent manner following abrogation of FAP+ CAF mediated immunosuppression, Professor Fearon justified such an approach as a novel therapeutic proposal to target PDA. The final session of the meeting was rounded off with prize giving; congratulations to Lisa Spary and Chris Hansell for best short talk and best poster prize, respectively.
After a buzzing drinks reception, discussions continued over a delicious conference dinner at the University Arms Hotel. This provided further opportunity to network with renowned names in the field of stromal immunology, and to ‘talk stroma’. Congratulations to the organisers for putting on a highly stimulating conference; here’s to next year’s meeting!