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Scientists discover novel modulator of human regulatory T cells

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LIRIL2R regulates FOXP3 expression and the ability to suppress iTregs. (A) Knockdown efficiency of two LNAs targeting the LIRIL2R transcript measured by TaqMan assay in 72-hour iTregs culture. (B and C) FOXP3 expression in LIRIL2R-silenced iTregs after 72 h. (D) Proliferation of responding cells after 72 hours of activation in the presence of LIRIL2R-sufficient (NT) or LIRIL2R-deficient (LNA1/LNA2) iTregs. (E) Quantification from five independent experiments, similar to that shown in panel D. Source: Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2315363121. https://www.pnas.org/doi/10.1073/pnas.2315363121

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LIRIL2R regulates FOXP3 expression and the ability to suppress iTregs. (A) Knockdown efficiency of two LNAs targeting the LIRIL2R transcript measured by TaqMan assay in 72-hour iTregs culture. (B and C) FOXP3 expression in LIRIL2R-silenced iTregs after 72 h. (D) Proliferation of responding cells after 72 hours of activation in the presence of LIRIL2R-sufficient (NT) or LIRIL2R-deficient (LNA1/LNA2) iTregs. (E) Quantification from five independent experiments, similar to that shown in panel D. Source: Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2315363121. https://www.pnas.org/doi/10.1073/pnas.2315363121

Professor Riitta Lahesmaa’s research group has discovered a new modulator of human regulatory T cells. This novel regulator can enhance or weaken the immune response and provides a new basis for therapeutic approaches in immune-related diseases.

The Lahesmaa group is based at the Turku Biology Center at the University of Turku and Åbo Akademi University in Finland and is part of the flagship research project InFLAMES.

T lymphocytes in our blood fight cancer, viruses and bacteria. Specific regulatory T cells are required to control abnormal immune responses, and disruption of their function may lead to autoimmune diseases or cancer.

Scientists have discovered a novel RNA that controls the development and function of regulatory T cells. This long intergenic non-coding RNA (lincRNA) modulates levels of the transcription factor FOXP3 and the suppressive function of human regulatory T cells by controlling the interleukin-2 receptor.

The research results are published in the journal Proceedings of the National Academy of Sciences. The discovery potentially enables the development of new therapeutic approaches to control the human immune response.

“Our discovery provides the basis for developing precise methods of treating autoimmune diseases and cancer. Regulatory T cells are already being studied in patients for the treatment of type 1 diabetes, and our new lincRNA molecule can, for example, be used to increase the production of these cells. cells for therapeutic purposes,” says Lahesmaa.

The discovery is particularly interesting because cancer cells are able to hide from the immune system by specifically manipulating regulatory T cells. Recently introduced therapeutic monoclonal antibodies for cancer, which are immune activators, attempt to break this concealment process.

Lahesmaa suggests that targeting the new lincRNA molecule could enable immune activation in cancer without the use of expensive antibodies.

LincRNA expression is highly tissue and cell specific, therefore targeting these molecules will enable precision therapy against desired targets.

More information:
Lahesmaa, Riitta, Long non-coding RNA LIRIL2R modulates FOXP3 levels and the suppressive function of human CD4+ regulatory T cells by regulating IL2RA, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2315363121. www.pnas.org/doi/10.1073/pnas.2315363121

Information about the magazine:
Proceedings of the National Academy of Sciences