Share 24. Mar. 2021
Press release;
An international team of scientists from CEITEC Masaryk University, and their colleagues from Russia and Israel, investigated the adaptive immunity of the blind mole-rat (Spalax Galili) – an animal that is striking in terms of its longevity, health span, and cancer resistance. The researchers revealed an unexpected organization of the Spalax adaptive immunity. The study with their findings was published in Nature Aging journal in February 2021.
The aging of the immune system is one of the critical factors of increased disease vulnerability associated with advanced age. The classical understanding of adaptive immunity implies memory. This memory is maintained within expanded clones of pathogen-specific B cells, helper T cells, and especially large expansions of cytotoxic T cells that may persist for months, years, or even a whole lifetime. These educated clonal expansions efficiently protect us from recurrent infections. At the same time, this also means that with aging, our adaptive immunity may accumulate the burden of erroneous decisions once made. The chronic activity of the misguided effector clones may contribute to what is called "inflammaging", associated with age-related diseases, including atherosclerosis, type II diabetes, and cancer.
In this study, the researchers focused on the immunity of a unique non-model organism Spalax Galili, a subterranean rodent inhabiting the eastern Mediterranean region. Similar to another famous non-model rodent, the naked mole-rat, Spalax has an extremely long lifespan – up to 20 years, which is ten times longer than for closely related mice and rats. In addition, Spalax and naked mole rats have demonstrated remarkable resistance to cancer. Although both animals share these unique features, they are evolutionarily distant and have developed diverse molecular mechanisms.
“Dr. Sharms, the head of the Israeli lab, has been working on Spalax for many years”, says Olga Britanova. “He has unique experience, including hunting the animals in the field (since they cannot be bred in captivity) and long-term maintenance of animal colonies. During the entire observation period (several decades), a colony of Spalax living in the vivarium together with several hundred animals showed no cases of spontaneous tumours. In addition, Israeli researchers discovered an exceptional resistance to chemically-induced cancer in Spalax. We’ve been studying the functions of adaptive immunity in aging and disease, including cancer, for many years, and this collaboration allowed us to investigate the immune organization in this distinctive non-model organism,” explains Olga Britanova.
The research groups revealed an unexpected organization of the Spalax adaptive immunity. Most strikingly, large clonal T cell expansions did not accumulate with the age of the Spalax, as they do in humans and mice. Furthermore, the expression of master transcription factors of T cell differentiation, checkpoints, and cytotoxic genes remained low through all Spalax ages. The immunoglobulin repertoire features a further suggested shorter B cell memory and sustained contribution of innate-like B cell response.
“The Spalax adaptive immune system 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,” conclude Dmitriy Chudakov and Olga Britanova.
In the future, the researchers are planning to investigate further the biology and immune system of Spalax using state-of-the-art experimental and computational methods.
To read the full publication click HERE.
The project funding was provided by the Russian Science Foundation (grant no. 16-15-00149, to O.V.B.), the Ministry of Education and Science of the Russian Federation (grant no. 14.W03.31.0005, to D.M.C., for part of mouse samples preparation), Israel Science Foundation (grant no. 1935/17, to I.S.), and M.M. was supported by the European Regional Development Fund– Project ‘MSCAfellow3@MUNI’ (grant no. CZ.02.2.69/0.0/0.0/19_074/0012727).
