Thread by @3DiMMUNE

a removal of a subset of #Tregs called T follicular regulatory cells (Tfr) from the immune system in #Foxp3-cre Bcl6-fl/fl mice #paradoxically reduces, rather than increases, #peanut-specific #IgE responses.

#immunology

bit.ly/2RAMe8L

And if you think maybe their knockout mice are some kind of weirdos, not really. Their model also shows that total IgE is increasing as expected. So, the system the authors are using is within acceptable norms.

bit.ly/2RAMe8L

The authors then went on to show that IL-10 derived from Tfr cells are important for promoting peanut allergy-producing IgE production. (IL-10 is lesser understood cytokine but it is generally accepted as an immunosuppressant.) #immunology

These results are totally against the whole paradigm about the role of Tfr cells and even IL-10 because the authors speculating that we need to block IL-10 to reduce peanut allergy rather than inject IL-10 to inhibit it, as everyone thinks currently.

So, how to interpret these results? Basically, what's going on? Is there a way to interpret these results within the confines of the established concept?

I think there is at least one possibility the authors did not consider in their discussions. Here the authors are looking for primary adaptive T/B cell response to a novel antigen, peanut antigen in this case.

bit.ly/2RAMe8L

In this scenario, peanut allergy promoting IgE response is clearly reduced without Tfr cells. But at the same time, the level of total IgE (representing unknown antigen-specific IgE responses) has increased.

We could say that total IgE is derived from an already established memory T/B system rather than from primary immune response as peanut IgE is. This memory T/B/plasma cells then boost total IgE levels when the brakes applied by Tfrs are removed.

But the same principle does not apply for primary T/B response to peanut allergen. Why is that? It is possible that the absence of Tfr specifically messes up with primary T/B cooperation.

bit.ly/2RAMe8L

It is not a direct effect but rather indirect due to the activation of other components of the immune system when brakes are removed. So, primary T/B responses will be undermined by a lack of Tfr cells and it would appear if Tfr cells were promoting primary IgE responses

and their absence reduced IgE production.

bit.ly/2RAMe8L

The correct interpretation is essential, especially when applied to human clinical data. In humans, peanut allergy IgE is already established as a memory system by the time the allergic individuals are examined by a doctor.

In that case, manipulation of the Tfr or IL-10 system the way the authors envisaged could be detrimental rather than beneficial.

bit.ly/2RAMe8L

@threadreaderapp unroll