Smashing up Smartphones: is there a better way?

Your immune cells are part of a powerful and complex coordinated system. You could think of it like a shiny new smartphone, all the pieces working together to respond when required. If your smartphone developed a fault and kept ringing or buzzing, refusing to turn off, what would you do?

Autoimmune diseases are caused by your immune system reacting when it shouldn’t. Cells and proteins that would normally be seen as safe are instead viewed as dangerous invaders, and attacked and destroyed. This leads to problems like type 1 diabetes, caused by your immune system attacking the cells which make insulin and keep blood sugar steady ,  multiple sclerosis, caused by attacks on nerve cells leading to muscle weakness, or rheumatoid arthritis, where misplaced inflammation causes joint pain and swelling.

So how do you fix the smartphone? Grab the nearest hammer and smash it until it stops? That wouldn’t be my first choice, but it’s the main option we have for treating autoimmune diseases. Medicines like steroids dial down your entire immune response, or certain treatments shut down specific cells. But when you destroy your phone you’ll miss the important calls too, just as these treatments leave patients vulnerable to infections and cancer, the very things your immune system usually protects you from.

Luckily we are making progress towards better ways to treat these diseases, as shown by a paper published last week in Nature. The authors decided that rather than smashing the smartphone, they would find a way to reprogram the part that has gone wrong. For many autoimmune diseases one of these parts is T cells. But if you remember from our roundup of immune cells, there is a special type of T cell called T regulatory cells which can keep the immune response in check. The researchers found a way to turn the self attacking T cells into regulatory T cells, which could reduce the symptoms of autoimmune diseases.

T cells need two switches flipping to turn them on properly. The first switch is the T cell receptor, which is flipped when it sees an antigen held up by an Antigen Presenting cell. The second switch comes from other parts of the Antigen Presenting cell sticking to parts of the T cell. When switch one is flipped without switch two, we used to think that the T cell basically went to sleep, stopped responding altogether. But now it looks like it might become a type of regulatory T cell, stopping the immune response to the antigen is has seen rather than encouraging it. The authors treated mice with beads coated with antigens in specialized holders called MHC. This improved the symptoms of mice with experimental versions of type one diabetes and multiple sclerosis. As we’ve mentioned before, mice aren’t humans. But to add extra encouragement to these results, the experiments also worked in mice which had their cells removed and replaced with human cells. If these hybrid mice can be helped by the nanobeads, then they may also have promise for human treatment. This research is still a long way from the clinic, but it looks like there is hope for our smartphone yet.



If you’d like more details on the experiments this Nature news and views article also talks about the work.





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