Distinct organization of adaptive immunity in the long-lived rodent Spalax galili

M. Izraelson, M. Metsger, A. N. Davydov, I. A. Shagina, M. A. Dronina, A. S. Obraztsova, D. A. Miskevich, I. Z. Mamedov, L. N. Volchkova, T. O. Nakonechnaya, M. Shugay, D. A. Bolotin, D. B. Staroverov, G. V. Sharonov, E. Y. Kondratyuk, E. V. Zagaynova, S. Lukyanov, I. Shams, O. V. Britanova, D. M. Chudakov

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

A balanced immune response is a cornerstone of healthy aging. Here, we uncover distinctive features of the long-lived blind mole-rat (Spalax spp.) adaptive immune system, relative to humans and mice. The T-cell repertoire remains diverse throughout the Spalax lifespan, suggesting a paucity of large long-lived clones of effector-memory T cells. Expression of master transcription factors of T-cell differentiation, as well as checkpoint and cytotoxicity genes, remains low as Spalax ages. The thymus shrinks as in mice and humans, while interleukin-7 and interleukin-7 receptor expression remains high, potentially reflecting the sustained homeostasis of naive T cells. With aging, immunoglobulin hypermutation level does not increase and the immunoglobulin-M repertoire remains diverse, suggesting shorter B-cell memory and sustained homeostasis of innate-like B cells. The Spalax adaptive immune system thus appears biased towards sustained functional and receptor diversity over specialized, long-lived effector-memory clones—a unique organizational strategy that potentially underlies this animal’s extraordinary longevity and healthy aging.

Original languageEnglish
Pages (from-to)179-189
Number of pages11
JournalNature Aging
Volume1
Issue number2
DOIs
Publication statusPublished - Feb 2021
Externally publishedYes

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