AIRE protein in the thymus directs expression of tissue-specific antigens that on one hand reduces number of auto-antigen specific T cell clones and on the other hand leads to generation of auto-antigen specific Foxp3+ regulatory T cells. However relationship between between central tolerance and its peripheral counterpart is not fully understood.
New study in Journal of Clinical Investigation examined relationship between hypomorphic AIRE function on Lyn-/- background. The authors found that such combination selectively accentuated eye-specific autoimmunity.
First, the authors observed that mice double deficient for AIREGW/+/Lyn-/- functions (but not single deficient) developed spontaneous eye inflammation.
These AIREGW/+/Lyn-/- mice showed expansion of eye-protein specific CD4 T cells and autoantibodies.
These auto-antigen specific T cells could infiltrate eye tissue causing inflammation.
The authors found that selective absence of Lyn in CD11c+ dendritic cells (AireGW/+CD11c-Cre Lynfl/fl) were sufficient to recapitulate this eye immunopathology.
Finally, the authors found that auto-antigen uptake by Lyn-/- DCs in eye draining lymph nodes contributed to eye inflammation.
In summary, this study indicates that some of the clinically relevant autoimmune phenotypes could be linked to failure to establish both central and peripheral tolerance.
David Usharauli
First, the authors observed that mice double deficient for AIREGW/+/Lyn-/- functions (but not single deficient) developed spontaneous eye inflammation.
These AIREGW/+/Lyn-/- mice showed expansion of eye-protein specific CD4 T cells and autoantibodies.
These auto-antigen specific T cells could infiltrate eye tissue causing inflammation.
The authors found that selective absence of Lyn in CD11c+ dendritic cells (AireGW/+CD11c-Cre Lynfl/fl) were sufficient to recapitulate this eye immunopathology.
Finally, the authors found that auto-antigen uptake by Lyn-/- DCs in eye draining lymph nodes contributed to eye inflammation.
In summary, this study indicates that some of the clinically relevant autoimmune phenotypes could be linked to failure to establish both central and peripheral tolerance.
David Usharauli
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