TRANSLATIONAL IMMUNOLOGY
Research Leader: Jo Jones
Overview:
The Jones lab is an experimental immunology group with a strong emphasis on translation. Our current key projects are as follows:
The Pan Immune Project (PIP)
Funding: Wellcome Trust Intermediate Followship/ Wellcome Trust Beit Prize
Jones’ Lab Team: Lorna Jarvis, Sarah Howlett, Dan Rainbow
Collaborators: Sarah Teichmann (Sanger Institute); Kourosh Saeb Parsy (Cambridge Biorepository for Translational Medicine), Menna Clatworthy (Cambridge).
Most of what is known about the human immune system comes from studying peripheral blood. However, given that much of our immune system resides in lymphoid organs and peripheral tissues, this is a very incomplete picture. To address this, we are performing single cell sequencing (5P/V(D J 10X genomics) of immune cells extracted from ~ 15 different lymphoid and non-lymphoid tissues (and matched blood) from deceased organ donors. This project is enabling us to understand how composition of the immune system varies across tissue sites within a single individual. We are also able to explore tissue specific signatures, clonal relationships across tissues and cellular interactions.
Immune Ageing
Funding: Chan Zucherberg Initiation (CZI)
Jones’ Lab Team: Lorna Jarvis, Sarah Howlett, Dan Rainbow
Collaborators: Nir Yosef (Berkeley), Donna Farber and Peter Sims (Columbia, Sarah Teichman and Roser Vento (Sanger Institute), Menna Clatworthy (Cambridge) and Muzlifah Haniffa (Newcastle).
By performing single cell sequencing (10X genomics) of immune cells extracted from multiple tissues from paediatric and adult deceased organ donors, this exciting new project will enable us to explore how the human immune system varies across the human lifespan. This project will also take a deeper dive into selected immune populations.
Tissue Regulatory Cells & Regulatory Cell metabolism
Funding: Wellcome Trust
Jones’ lab team: Lorna Jarvis, Sarah Howlett, Dan Rainbow
Collaborators: Tissue Regulatory cells – Valerie Coppard; Cell metabolism – Luca Peruzzotti-Jametti (Cambridge)
In these two closely related projects we are exploring the T regulatory cell compartment in human tissues (see PIP above), and how regulatory cells alter their metabolism in order to cope with the increased demands of activation and proliferation.
Understanding the immunogenicity of regenerative cellular therapies
Funding: MRC – UK Regenerative Medicine Platform; Rosetree’s Trust
Jones’ Lab Team: Sarah Howlett
Collaborators: Giovanna Lombardi (King’s); Kourosh Saeb Parsy (Cambridge) and Roger Barker (Cambridge)
The aim of this project is to develop robust in vitro and in vivo models (using mice transplanted with a human immune system) to test the immunogenicity of human pluripotent stem cell derived cellular therapies. In particular the Jones’ group is focused on determining the immunogenicity of embryonic stem-cell (ES)-derived dopaminergic cells. Although being developed as a treatment for Parkinson’s disease, it is not yet known whether these cells will be rejected by the patient’s immune system following transplantation, in the same way that mismatched solid organ transplants would be. The results of our work will inform upcoming clinical trials.
The Biological Basis of GWAS hits for Multiple Sclerosis (MS)
Funding: Rosetree’s Trust and the Cambridge Trust
Jones’ Lab Team: Hani Mousa
Collaborators/Advisors: Linda Wicker (Oxford)
MS is an autoimmune disease of the central nervous system in in which focal lymphocytic infiltrates lead to myelin and axonal damage. Disease susceptibility is partially dependent on genetic background: first-degree relatives of people with MS have a 10-fold higher risk of developing the disease, which increases to 200-fold in identical twins. To understand this link, several genome-wide association studies (GWAS) have been performed, resulting in the identification of > 200 disease-associated Single Nucleotide Polymorphism (SNPs). In this project (led by PhD student Dr Hani Mousa) we have studied, and identified several biological consequences of the variant in LIGHT (TNFSF14) and its receptor HVEM (TNFRSF14) – particularly in cells of the myeloid lineage.
The Role of Low-dose IL-2 in promoting Tregs post-immunodepletion
Funding: Wellcome Trust PhD Studentship (Zoya Georgieva); Sanofi-Genzyme Investigator Award
Jones’ Lab Team: Zoya Georgieva, Sarah Howlett
Collaborators/Advisors: Alasdair Coles (Cambridge) Linda Wicker (Oxford)
The anti-CD52 lymphocyte depleting monoclonal antibody, alemtuzumab (Lemtrada) is a highly effective treatment of relapsing-remitting MS; however ~50% of patients develop a new autoimmune disease (primarily thyroid) as their immune system recovers after treatment. In this PhD project (led by Dr Zoya) using a combination of in vitro assays and a CD52tg mouse model, we are exploring whether or not low-dose IL-2 is capable of selecting expanding regulatory T-cells post-alemtuzumab, with the longer-term hope that this might reduce the autoimmune complications of Lemtrada.