MS is the result of immune cells attacking the protective sheath surrounding nerve fibres in the brain and spinal cord. The cell type that orchestrates the attack in MS and in laboratory models of the disease is known as T helper 17 (Th17) cells. Normally, Th17 cells protect the body against infections of bacteria and some fungi.
Some existing treatments act by eliminating another type of immune cell, known as B cells, but also reduce the numbers of Th17 cells, potentially compromising the immune protection against infections.
This project will improve our understanding of how Th17 cell development is controlled and the role of B cells in this development process. This will identify ways to enhance therapies for MS and improve immune defence against infections in people with MS receiving B cell depleting therapies.
This project aims to better understand the contribution of B cells to the generation and activity of Th17 cells that are key players in causing the damage in MS. Since Th17 cells are also required to protect the body from infections, the first aim of this study was to investigate the involvement of B cells in Th17 immune responses after exposure to bacteria. Dr Liu found that those mice with B cells were better at clearing the bacteria infecting their lungs, compared with mice that had no B cells. Dr Liu and colleagues also found that that the number of Th17 cells were also increased as these mice became infected with bacteria, however, this increase was much more subtle in those mice that were lacking B cells. These preliminary results suggest that B cells are important for protection against bacterial infections and may also be important for generating a Th17 response.
Interleukin 21 (IL-21) is a chemical messenger that has been shown to influence immune responses. It is a key protein produced by Th17 cells as well as B cells. Examining autoimmune disease in mice, we found that mice unable to produce or respond to IL-21 showed less severe and delayed disease. Furthermore, these mice produced fewer Th17 cells during inflammation compared to mice that did have B cells. These findings suggest that IL-21 may be a promising target for MS therapy.
Dr Liu has also undertaken specialist work to create optimised assay conditions for generating Th17 cells from human samples, in preparation for testing cells from the blood of MS patients. The goal of these analyses are to compare the levels of Th17 cells between people with B-cell deficiencies and healthy controls.
Now continuing the project, Associate Professor Cecile King and Dr Loetsch will use these assays established by Dr Liu to analyse the interactions and activities of B-cells and Th17 cells in human blood samples from people with B-cell deficiencies in comparison to healthy blood donors.
Dr Loetsch will also be collaborating with investigators at the Garvan Institute and St Vincent’s Centre for Medical Research in Sydney to look at the interaction of B cells and Th17 cells in mice with an MS-like illness known as experimental autoimmune encephalitis (EAE).
This important work will increase our understanding of how B cells regulate Th17 cell development and activity. Being able to distinguish the interactions of B cells and Th17 cells will be a step towards the use of more tailored applications of existing B cell targeted therapies, and the development of novel and specific therapies for MS, whilst limiting the detrimental effects to our immunity.
Updated: 8 June 2016
Updated: 06 January, 2013