Sunday, September 20, 2015

Perforin deficiency in dendritic cells leads to overweight and metabolic syndrome

Dendritic cells (DCs) are both necessary for immunity and tolerance. While immunity part is more or less clear, DC's role in tolerance is not clear at all.

Here is another weird tolerogenic DC paper from Immunity. Here, the authors found that in BM chimera mice that lack perforin specifically in CD11hi DCs develop a metabolic syndrome (obesity, insulin resistance and low glucose tolerance).

To tell you truth, this study should not be in Immunity. Journal of Immunology would have been better place. The problem is that the authors did not even bother to check any role of gut micirobiota in all these. But if you mention metabolic syndrome and did not check for gut microbiota, this is a cardinal sin for today's immunology.

In brief, the authors have generated mixed BM chimera mice wherein only DCs in mouse would be derived from BM cells lacking perforin (though having CD11c-driven Cre model would have been better alternative). Unexpectedly, the authors found that starting at 3 month these BM chimera mice become overweight.

The authors found that these mice with CD11c-specific perforin deficiency developed large adipose cells.

Finally, they showed that metabolic syndrome in these mice could be reversed by T cell depletion (but the authors have no data to explain why or how presence of T cells induces metabolic syndrome).

In summary, according to authors, this study suggests that when DCs lack perforin and are not able to eliminate T cells, this leads to accumulation of T cells that promote metabolic syndrome. What or how is not known. No words about gut microbiome.

David Usharauli  

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