Wednesday, November 16, 2016

Part of AIRE KO phenotype (APECED in humans) is dictated by gamma-delta T Cells

AIRE deficiency in mice (human equivalent of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, APECED) leads to chronic tissue immunopathology. Due to role of AIRE in generation of thymic FOXP3+ T regulatory cells, it is believed that underlying cause for tissue pathology on AIRE KO background is a lack of Tregs specific for tissue specific antigens.

However, the new data in journal Immunity from the research group which pioneered the study of AIRE suggest that part of AIRE KO phenotype is dictated by changes in γδ T cells secreting cytokine IL-17.

The authors observed that while total γδ T cells numbers were not different WT and AIRE KO littermates, γδ T cells expressing IL-17 were up-regulated in AIRE KO mice.



Interestingly, AIRE KO mice also deficient for γδ T cells (double deficient mice) showed marked resistance to immunopathology to such tissues as eyes and lungs (though other target tissues were still susceptible).



At the cellular level, there was a significant increase in IL-23r-GFP+ γδ T cells (marker for IL-17+ γδ+ T cells) in retinal tissue in AIRE KO mice at early age, even before tissue pathology was apparent. Of note, the fact that IL-17+ γδ+ T cells are present in retinal tissue in WT mice as well points to its role in physiological processes, not just in pathology).



In summary, this study indicates that subset of γδ T cells could play a leading role in initiating certain tissue pathology on AIRE KO background.

It is not clear, however, how changes in γδ T cell compartment relates to changes in Treg compartment on AIRE KO mice. Also, the role of tissue microbiota and its changes in KOs should be considered to fully understand immunopathologies. In this paper the authors provided the answers to neither to these two relevant topics.

David Usharauli


1 comment:

  1. Great article, Dave. I haven't read the paper but do they say anything about Loss of function/ rescue function using specific subsets of gdTcells? I'm guessing it's Vg9Vd2 since it's IL17 producing. This is very interesting finding. Have to read the paper now.

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