You may not know this, but this owlette is a (reformed) scientist. As I have missed looking through cool papers and writing about them, I have decided to take a stab at writing a little science blog here (I have yet to decide on the tone, perhaps it will depend on the paper).
And what best way to start than with a paper from my former lab that I saw this morning in Nature Communications. I realise that I am probably shooting myself in the foot, as this is quite a complicated paper on immunology, a discipline that everyone seems to be scared of and find incredibly confusing. But I never said I didn't like jumping in the deep end! I promise, it is a cool story and I will try and keep it simple.
The immune system is actually a beautifully complicated network of cells (including various types of T cells, B cells, dendritic cells etc) that travel around the highways of the blood stream and lymphatic system to fight infection. It is true, through the years it has become increasingly complicated with the different cell types discovered (bordering on the ridiculous now, I have lost track). But ask any immunologist and they will declare their undying love for their favourite cell type.
The lab I did my PhD in had an interest in how one type of immune cell, known as an effector T cell (named as such because it actually does the work), knows where to go during its journey through the body. What had become apparent is that during their travels, effector T cells are eventually 'told' to stop by the cells lining the blood vessels. These cells, called endothelial cells, use a molecule known as major histocompatibility complex II (MHC II) to present antigen (what the T cells are interested in) to the T cells. This makes the T cells slow down to scan these antigens until they find the one they are looking for (ie the one they are specific for). At this point, they can finally cross the blood vessel and enter the tissue to carry out their functions.
To make sure that they don't create chaos and start attacking the body instead of invaders, there are numerous checks and balances that, among others, educate the cells to what constitutes 'self' and also stop them from getting out of control. One of the checks and balances are another type of T cell known as a regulatory T cell (TReg). There are generally very few of these in the body, and it had previously been shown that, to stop inflammation, at least in the context of transplants, 30% of the infiltrating T cells need to be TRegs. And yet, despite their low frequency, they still manage to get to the tissue in sufficient numbers and regulate effector T cells. So how do the TRegs do this?
As it turns out, TRegs are also guided to specific tissues by endothelial cells. Through a range of experiments, including blocking MHC II molecules and therefore antigen presentation, the authors here demonstrate that endothelial cells once again display antigen to TRegs. These can now find the target tissue and migrate there in a fast and efficient manner.
But the key finding I think in this paper is that, once the TRegs have infiltrated the tissue, they can then block the recruitment of effector T cells. This pressumably allows them to dampen any further effector responses as they reach the aforementioned 30% ratio of effector T cells: TRegs.
Although exactly how this is achieved requires further investigation, a better understanding of the molecular basis of this process could have an incredible impact, for example to help prevent the rejection of allotransplants and to control autoimmunity in specific tissues.
And what best way to start than with a paper from my former lab that I saw this morning in Nature Communications. I realise that I am probably shooting myself in the foot, as this is quite a complicated paper on immunology, a discipline that everyone seems to be scared of and find incredibly confusing. But I never said I didn't like jumping in the deep end! I promise, it is a cool story and I will try and keep it simple.
The immune system is actually a beautifully complicated network of cells (including various types of T cells, B cells, dendritic cells etc) that travel around the highways of the blood stream and lymphatic system to fight infection. It is true, through the years it has become increasingly complicated with the different cell types discovered (bordering on the ridiculous now, I have lost track). But ask any immunologist and they will declare their undying love for their favourite cell type.
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| How could you not love this T cell beauty? Image from NIAID (https://www.flickr.com/photos/niaid/5950870236/) |
The lab I did my PhD in had an interest in how one type of immune cell, known as an effector T cell (named as such because it actually does the work), knows where to go during its journey through the body. What had become apparent is that during their travels, effector T cells are eventually 'told' to stop by the cells lining the blood vessels. These cells, called endothelial cells, use a molecule known as major histocompatibility complex II (MHC II) to present antigen (what the T cells are interested in) to the T cells. This makes the T cells slow down to scan these antigens until they find the one they are looking for (ie the one they are specific for). At this point, they can finally cross the blood vessel and enter the tissue to carry out their functions.
To make sure that they don't create chaos and start attacking the body instead of invaders, there are numerous checks and balances that, among others, educate the cells to what constitutes 'self' and also stop them from getting out of control. One of the checks and balances are another type of T cell known as a regulatory T cell (TReg). There are generally very few of these in the body, and it had previously been shown that, to stop inflammation, at least in the context of transplants, 30% of the infiltrating T cells need to be TRegs. And yet, despite their low frequency, they still manage to get to the tissue in sufficient numbers and regulate effector T cells. So how do the TRegs do this?
As it turns out, TRegs are also guided to specific tissues by endothelial cells. Through a range of experiments, including blocking MHC II molecules and therefore antigen presentation, the authors here demonstrate that endothelial cells once again display antigen to TRegs. These can now find the target tissue and migrate there in a fast and efficient manner.
But the key finding I think in this paper is that, once the TRegs have infiltrated the tissue, they can then block the recruitment of effector T cells. This pressumably allows them to dampen any further effector responses as they reach the aforementioned 30% ratio of effector T cells: TRegs.
Although exactly how this is achieved requires further investigation, a better understanding of the molecular basis of this process could have an incredible impact, for example to help prevent the rejection of allotransplants and to control autoimmunity in specific tissues.
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