Friday, March 27, 2015

First-born thymic Foxp3+ regulatory T cells protect against tissue-selective AIRE-dependent autoimmune syndrome

Adaptive immune system should be able to distinguish between self and non-self antigens. This is a very fine process since at the molecular level both self and non-self antigens look the same. So how it is done?

AIRE is a gene that controls tissue-specific protein expression in the thymus. The authors observed that conditionally T reg-depleted neonatal mice supplemented with T regs from AIRE KO donor, but not from WT donor, developed tissue-specific autoimmune syndrome.

Further experiments with adoptive transfer of T reg population tagged either during neonatal stage (day 0-10) or after weaning (day 35-45) revealed that only neonatally tagged T regs were enriched in Foxp3+ population able to prevent the development of AIRE-dependent tissue-selective autoimmune syndrome.

The results from this study suggest that the role and functionality among Foxp3+ T regs varies depending, at least, on time of their generation. It appears that first-born T regs generated during a neonatal stage provide specialized protection against development of autoimmune syndrome (though tagging per se did not specifically identify AIRE-driven Foxp3+ T regs in newborn mice in this study).

Interestingly, the authors reported that in NOD.Foxp3-DTR mice T reg depletion after weaning did not result in death of the experimental animals. This is in contrast to earlier reports from Rudensky's lab where adult Foxp3-DTR mice die after T reg depletion. Wonder what could have made such difference.   

David Usharauli

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