Research press release


Nature Medicine

Aging impairs T cell immune responses


Jorgo Goronzyたちは、若者のCD4+T細胞に比べると高齢者のCD4+T細胞は、少量の抗原や親和性の低い抗原に対する応答能力が低いことを明らかにした。このT細胞受容体情報伝達に対する感受性の低さに関係していたのが、miR-181aの発現の低下とその標的の1つであるDUSP6の発現の亢進で、どちらもこれまでに、T細胞受容体からの情報伝達能に関係することが報告されている。Goronzyたちは、DUSP6の発現や機能を阻害すると、高齢者由来のCD4+T細胞の応答が改善されることを発見した。この経路を標的にすれば、高齢者のワクチンに対する反応が良くなる可能性がある。

The responses of specific immune cells, CD4+ T cells, are impaired with age due to the reduced expression of a microRNA which helps regulates the phosphatase DUSP6, important for fine-tuning T cell sensitivity to antigen. The findings, published online this week in Nature Medicine, suggest that DUSP6 could be a target to improve T cell immune responses in the elderly.

In people, T cell function declines with age, reducing protection from vaccines and increasing susceptibility to infection, but it is unclear how the impaired response of CD4+ T cells occurs.

Jorg Goronzy and colleagues show that CD4+ T cells from elderly individuals are less able to respond to antigens at low dose or of low affinity compared to CD4+ T cells from younger people. This reduced sensitivity to T cell receptor signaling was associated with decreased expression of miR-181a and increased expression of one of its targets, DUSP6; both have been previously linked to T cell receptor signaling potency. The authors found that inhibition of DUSP6 expression or function ameliorated responses of CD4+ T cells from older individuals, suggesting that targeting this pathway might improve vaccine responses in this population.

doi: 10.1038/nm.2963


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