The immune system is complex and made up of many different types of cells that keep each other in check. As we don’t yet know which parts of the immune system are acting out of line in alopecia areata, more research into these mechanisms is crucial. At the University of Glasgow, researchers have been hard at work to study the role of the immune system in alopecia areata.

Previous work

In 2017, Professor Simon Milling from the School of Immunity & Infection at the University of Glasgow was awarded funding from AAR-UK (now merged with AUK) to set up research on the relationship between the gut, the immune system, and alopecia areata. It led to the creation of the Alopecia Biobank, which hosts hair, skin and blood samples kindly donated by volunteers with alopecia areata (AA). As a PhD student in Simon’s lab, Kym Bain used some of these samples to investigate differences in the activity of the immune system in people with and without AA. This work was published in 2020. More recently, she has also looked at the immune cells that live in blood, and at the bacteria that live in our intestine and form a large part of our ‘intestinal microbiota’. She previously wrote blogs about her work in 2018, 2019 and 2021.

Kym’s work on this project has now concluded, and her second research article was recently published in the Journal Clinical and Experimental Immunology. In short, Kym and her team studied the levels of specific types of immune cells in blood samples, aiming to find differences between people with and without AA. Within the group of people with AA, they also looked at the differences between those with and without an allergy-related condition such as atopic dermatitis or allergic asthma. By studying which types of cells are behaving differently in people with AA, they aimed to better understand what is leading to the hair cells being attacked. What they found was that some types of immune cells “B cells” were present in higher amounts in people with AA, particularly those with allergic conditions and those with extensive hair loss (>50% SALT score, measured using the Severity of Alopecia Tool). In people with  less severe hair loss (<50% SALT), different immune cells “T cells” were found to be more common. Based on this, they suggest that immune therapies that target T cells may be more effective in people with SALT scores <50%. So, it may be important to deliver these therapies early before AA is allowed to develop further.

What’s happening now?

Recently, Professor Milling has received funding from the Office of the Chief Scientific Adviser (Scottish Government) to further investigate the role of different immune processes in alopecia areata. Some of this funding is specifically for work on macrophages, which are one type of immune cell that defend against dangerous substances inside the body. Macrophages are found in all tissues of the body. They function as immune cells, where they behave a bit like Pac-Man, as they swallow materials they come into contact with and destroy them. Because of this, they are very good at killing infectious bacteria that may get through the skin, for instance in a wound.

An electron microscope image of a macrophage next to the popular 80s game Pac-Man. Left image credit: S. Gordon, 2007, European Journal of Immunology.

Macrophages also have many other functions in the body, depending on the tissue in which they are located. In the skin they play important roles in helping to heal wounds, and they are also closely associated with hair follicles. In healthy skin they help to control the hair cycle, but in AA this function may be disrupted, contributing to persistent hair loss. Following on from the published work, Professor Milling has also received funding to look more closely at the role played by T cells in the skin of people with AA. T cells are the immune cells that have overall control of the immune response, and so these skin T cells may provide important clues to understanding how to improve therapies for AA. The macrophage work is being carried out by Alana Brown, and the T cell project by Eleanor Richards.

Alana Brown is a researcher working on the macrophage project in Professor Milling’s lab. Her work will analyse parts of the genetic code expressed by individual macrophage cells (something called single-cell sequencing) to find out which genes are up- or down-regulated in people with AA. Immune cells such as macrophages can be influenced by their local environment, for example by receiving signals from other immune cells. These signals can then switch on or off specific parts of the genetic code. As genes code for specific proteins, that perform specific functions, identifying which genes are involved can help us identify the processes that drive hair loss in alopecia. The single-cell sequencing will be performed on skin samples from areas of established AA, where there is no hair growth, and areas of active AA, where there is active hair loss. Looking at the differences, if any, between these sample types will allow us to better understsand the mechanisms which drive hair loss and those which maintain hair loss. Along with single-cell sequencing, Alana will use a technique called "immunohistochemistry" to determine which proteins macrophages are expressing and their location in and around hair follicles. The aim of this project is to find out which parts of the macrophage genetic code are differently expressed between people with and without AA, and in affected and unaffected parts of skin in the same person.

Eleanor Richards (Elle) is a PhD student with a passionate interest in autoimmunity and related conditions which has led her to research alopecia areata with Professor Simon Milling. Elle has recently started working on mapping out immune cell activity in skin. By colour staining slices of skin using specific markers, she will be able to identify different immune cell types under a microscope. In addition, the skin will be broken down into individual cells. Fluorescent substances are then added to the surface of the cells, which means they will light up when they are analysed in a device called a “flow cytometer”. This will then allow identification of the types of immune cells and the amounts of each in the skin. As in Alana’s project, the cells will also go through single-cell sequencing to identify any differences in their expressed genes.

Elle is particularly interested in the differences between the centre and the edge of a patch of hair loss, which might be affected differently by the immune response. Through this project, she is hoping to find targets for treatment in the area of hair loss. Specifically, Elle is looking into the role of CD8 positive T cells, which are a group of immune cells that help to regulate the hair growth cycle and macrophages.

The research team are still looking for samples from people with and without AA. By comparing samples from people with and without AA, we can learn more about what parts of the immune system are causing the hair loss. If your family members or friends have always wanted to contribute to alopecia research but have never had the chance, now may be the time to get in touch with [email protected] to see if you can help out (note that the research lab and clinic are in Glasgow).

To learn more about immunology, BiteSized Immunology by the British Society for Immunology is a great resource.