Autoimmune rheumatologic diseases

Poster

In Active Juvenile Idiopathic Arthritis the Synovial Microenvironment May Shape a Discordant Transcriptome Profile in Pathogenic Immune Subsets from a Common Precursor

Friday, June 16
6:15 PM - 7:30 PM

We have previously identified T cell subsets in both Teff (CPLs) and Treg (iaTreg) compartments that are HLA-DR positive, antigen experienced, pro-inflammatory, correlating with disease activity and sharing strong TCR oligoclonality with synovial T cells. Their phenotype and association with clinical fate inspired out current hypothesis that these functionally discordant cells may originate from a common precursor. Next generation RNA sequencing was performed on sorted CPLs (CD3+ CD4+ CD14- HLADR+ CD25/CD127 Teff gate) and iaTregs (CD3+ CD4+ CD14- CD25hi CD127lo Treg gate) from 8 active disease JIA patients. Comparative analysis between CPLs vs iaTreg and that of the common pool of Teff vs Treg, indicate a dramatic reduction from 916 to only 143 unique gene regulation despite functional lineage differences, suggesting strong microenvironment influences. TCR sequence oligoclonality in CPLs/iaTregs versus that of the common Teff/Treg pool reinforce the possibility of a common precursor. Deep immuno-phenotyping revealed commonality in the dysregulation exhibited in both CPLs and iaTreg, notably perturbations in TCR/PD1 signalling and IFN-g pathways. The retention of 143 conserved differentially regulated genes (immune response, apoptosis, intracellular signalling and metabolic processes) between CPLs and iaTregs provide insights to the pathways pertinent to pathogenesis and may identify targets of therapeutic value. Intriguingly, as both subsets transit in the inflamed synovium, these data underscore a potential role of the microenvironment in shaping two functionally dichotomic populations from a common precursor.

Jing Yao Leong

Research fellow
SingHealth Translational Immunology and Inflammation Centre

Presentation(s):

    Send Email for Jing Yao Leong

    Pavanish Kumar

    Research fellow
    SingHealth Translational Immunology and Inflammation Centre, Duke-NUS Graduate Medical School, Singapore

    Presentation(s):

      Send Email for Pavanish Kumar

      Phyllis Chen

      SingHealth Translational Immunology and Inflammation Centre, Singapore Health Services Pte Ltd

      Presentation(s):

        Send Email for Phyllis Chen

        Joo Guan Yeo

        SingHealth Translational Immunology and Inflammation Centre

        Presentation(s):

          Send Email for Joo Guan Yeo

          Camillus Chua

          SingHealth Translational Immunology and Inflammation Centre, Singapore Health Services Pte Ltd

          Presentation(s):

            Send Email for Camillus Chua

            Suzan Saidin

            SingHealth Translational Immunology and Inflammation Centre, Duke-NUS Graduate Medical School, Singapore

            Presentation(s):

              Send Email for Suzan Saidin

              Justin Tan

              Consultant, Rheumatology and Immunology Service
              KK Women’s and Children’s Hospital

              Presentation(s):

                Send Email for Justin Tan

                Thaschawee Arkachaisri

                Senior Consultant and Head of Rheumatology and Immunology Service
                KK Women’s and Children’s Hospital and Duke-NUS Graduate Medical School Singapore

                Presentation(s):

                  Send Email for Thaschawee Arkachaisri

                  Alessandro Consolaro

                  Second Paediatric Division, University of Genoa and G Gaslini Institute

                  Presentation(s):

                    Send Email for Alessandro Consolaro

                    Marco Gattorno

                    UOC Pediatric Rheumatology, Lab Immunology Rheumatic Diseases, IRCCS Istituto Giannina Gaslini, Genoa, Italy

                    Presentation(s):

                      Send Email for Marco Gattorno

                      Alberto Martini

                      University of Genoa and G Gaslini Institute

                      Presentation(s):

                        Send Email for Alberto Martini

                        Salvatore Albani

                        Director
                        SingHealth Translational Immunology and Inflammation Centre, Duke-NUS Graduate Medical School, Singapore

                        Presentation(s):

                          Send Email for Salvatore Albani


                          Assets

                          In Active Juvenile Idiopathic Arthritis the Synovial Microenvironment May Shape a Discordant Transcriptome Profile in Pathogenic Immune Subsets from a Common Precursor



                          Attendees who have favorited this

                          Send Email for In Active Juvenile Idiopathic Arthritis the Synovial Microenvironment May Shape a Discordant Transcriptome Profile in Pathogenic Immune Subsets from a Common Precursor