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Fibroblastic cells and their utility

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Section of a human tonsil depicting T cells (green) interacting with the FRC structural cells (red). COX2 (blue) is part of one of the mechanisms that the structural cells use to control T cells (green).

I get asked a lot about our cells and what they do. They are actually less known than I would like them to be and this prompted me (together with today’s publication of our paper in PLoS Biology) to write this little post on what are they do and how they can be useful in a variety of research questions.

It is important to first describe what fibroblasts are. They are a cell type that can be found all over the body that usually performs a structural support role for other cells to perform their role. That is not to say that they have no function of their own, they clearly do, and in fact, some fibroblasts are highly specialized (e.g. cardiac fibroblasts). However, not all fibroblasts are the same, as skin fibroblasts are different from myofibroblast that are different from lymph node fibroblasts.

One would think that the abundance of these cells would mean that people paid more attention to them. They are, but the global picture is sometimes missing. An overlooked aspect is how these cells are forming a support cellular highway for other cells to interact and localize to. These cells are not static but very dynamic in their signalling cascade “telling” immune cells were to gather or bringing them together to interact. Other times they can prime immune cells by gathering from their environment substances and showing them to the inquisitive immune cells. This can help in educating the immune cells on what is foreign and what is self, preventing autoimmunity or priming the cell for a foreign intruder.

In our paper linked above, we have also found that Fibroblasts have also the ability to suppress cells. Lymph node fibroblasts put the brakes on T cells momentarily preventing them from proliferating near them. As soon as they are away from the fibroblasts T cells continue to do their job if they encounter another stimulus. This suppressive effect is mediated by soluble factors and is reversible by inhibitors.  So now we have a cell type that can control T cells and that we can manipulate in the test tube to switch the suppressive effect on or off. Maybe not just in the test tube though…

One of our latest experiments is done using tonsils. Tonsils, in case you are wondering, are lymph nodes.  Some people get them removed for various medical reasons (sleep apnea, repeated infections etc.). For years activation of T cells in this tissue was thought to be difficult to achieve. When you stimulate T cells to provoke them to proliferate in tonsil nothing happens. However, we show, for the first time, that if you use the inhibitors for the fibroblasts and then try to stimulate them, now you can actually see the T cells proliferating quite substantially. This is in a live tissue sample straight from the clinic. Very exciting and it opens up so many possibilities.

Think about all the different drugs and antibodies that can be tested. These are designed to activate/dampen immune cells but we have no idea how they behave in the human body without going through mouse trials and then human trials. This could be used as an intermediate link, offering higher confidence for potential therapies. You could test your therapy in live tissue to observe the effect and screen for things like toxicity, activation, suppression, differentiation etc.

I hope that this shows how important fibroblasts can be. We are actively pursuing many questions in our lab that you can find here. They are all related to Fibroblasts and their interaction with the immune system. We are excited to share our stories so check back here from time to time for updates.

–Konstantin Knoblich

 

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