Stopping T cells entering the brain in MS

Dr Iain Comerford

University of Adelaide

February 2022

specialisation: Immunology

focus area: Better treatments

funding type: Fellowship

project type: Investigator Led Research

Summary

In MS, cells of the immune system enter the brain and spinal cord and produce substances that cause inflammation, resulting in damage that leads to the disease symptoms. Understanding how the immune cells enter the brain is likely to lead to better therapeutics that can interfere with this process.   

This project will focus on the ways in which inflammatory immune cells called T cells, enter the brain. New ways to block inflammatory T cell migration will be tested and the disease-causing T cells will be examined in more detail in this study.  

This project should identify new ways in which MS may be better treated in the future.  

Progress

Dr Comerford and his team have developed new laboratory models to study the effect of the body’s own immune signals on the disease-causing ability of T cells. They have found several molecules used by cells of the immune system that promote or inhibit inflammatory T cells and their movement into the brain. It is hoped that by blocking or stimulating the paths these T cells take, the team can discover new and more effective ways to reduce inflammation in the brain during MS.

Dr Comerford and his team have also assembled two collections of genes: one that controls how cells move and another that controls T-cell proteins that help turn specific genes on or off.

Over the next 12 months, Dr Comerford and his team will study the mechanisms by which some molecules control the disease functions of T cells. They will test other laboratory models for use in studying the fate of disease-causing Th17 T cells. The team will also continue analysing data produced from single cell CITEseq (a data set of genetic codes for proteins) to produce hypotheses that can be tested regarding new combinations of molecules that govern the movement of disease-causing T cells. New Pro-Codes technology is being established in Dr Comerford’s laboratory to further study Th17 T cells and their movement into the central nervous system.

publications

  • Heng AHS, Han CW, Abbott C, McColl SR and Comerford I. Chemokine-driven migration of pro-inflammatory CD4+ T cells in CNS autoimmune disease. Frontiers in Immunology. 2022. 13:817473 
  • Bastow CR, Kara EE, Tyllis TS, Vinuesa CG, McColl SR and Comerford I. Tfr cells express functional CCR6 but it is dispensable for their development and localisation during splenic humoral immune responses. Frontiers in Immunology. 2022. 13:873586 
  • Foeng J, Comerford I and McColl SR. Harnessing the chemokine system to home CAR-T cells into solid tumours. Cell Reports Medicine. 2022. 3(3):100543  
  • Bandara V, Foeng J, Gundsambuu B, Norton TS, Napoli S, McPeake DJ, Tyllis TS, Rohani-Rad E, Abbott C, MillsSJ, Tan LY, Thompson EJ, Willet VM, Nikitaras VJ, Zheng J, Comerford I, Johnson A, Coombs J, Oehler MK,Ricciardelli C, Cowin AJ, Bonder CS, Jensen M , Sadlon TJ, McColl SR, Barry SC. Pre-clinical validation of a novel pan-cancer CAR-T cell immunotherapy targeting nfP2X7. Nature Communications. 2023. 
  • Abbott CA, Freimayer EL, Tyllis TS, Norton TS, Alsharifi M, Heng AHS, Pederson SM, Qu Z, Armstrong M, Hill GR,McColl SR and Comerford I. Determination of Tr1 cell populations correlating with distinct activation states in acute IAV infection. Mucosal Immunology. 2023 S1933-0219(23)00048-X. 

Accepted for publication

  • Comerford I and McColl SR. Atypical chemokine receptors in the immune response. Nature Reviews Immunology.  

Updated 31 March 2024 

lead investigator

total funding

$390,000

start year

2022

duration

3 years

STATUS

Current project

Stages of the research process

Fundamental laboratory Research

Laboratory research that investigates scientific theories behind the possible causes, disease progression, ways to diagnose and better treat MS.

Lab to clinic timeline

10+ years

Translational Research

Research that builds on fundamental scientific research to develop new therapies, medical procedures or diagnostics and advances it closer to the clinic.

Lab to clinic timeline

5+ years

Clinical Studies and Clinical Trials

Clinical research is the culmination of fundamental and translational research turning those research discoveries into treatments and interventions for people with MS.

Lab to clinic timeline

3+ years

Read More

Newsletter subscription

  • Enter your details

Stopping T cells entering the brain in MS