The intra- and extracellular landscape of human regulatory T cells in health and heart disease

Paola de Candia, PhD
Researcher
Department of Molecular Medicine and Medical Biotechnologies
University of Naples Frederico II
Naples, Italy

This conference is hosted by May Faraj, PhD. This conference is part of the 2024-2025 IRCM conference calendar.

About this conference
Human forkhead-box-P3 (FoxP3)+CD4+CD25+ regulatory T (Treg) cells are key players in the control of immunological self-tolerance, and hence enormous interest is dedicated to understanding the biology behind their growth and function. In vivo, Treg cells have a high anabolic state, reside in crucial body districts, recirculate between lymphoid and non-lymphoid sites, and show unique intrinsic capacity to perceive nutritional changes. The well-known Treg in vitro anergy can be reversed by signals of pseudo-starvation, which unlock Treg proliferation also through the induction of the redox controller cystine/glutamate antiporter solute carrier (SLC)7A11. This induction is impaired in people with relapsing-remitting multiple sclerosis (pwRRMS), a defect that may contribute to the progressive loss of Treg cells in that autoimmune disease.

In terms of immunosuppressive ability, we have more recently shown that Treg cells curb CD4+ conventional T (Tconv) cells also through the release of extracellular vesicles (Treg-EVs) shuttling specific miRNAs that down-regulate mRNAs necessary for Tconv cell growth and effector functions, such as SLC7A11 itself. Notably, Treg-EVs from pwRRMS contain a dysregulated miRNA cargo and show a diminished inhibitory effect.

In conclusion, while proliferation and function are traditionally perceived as separated in Treg cells, we propose that their capability to engage anabolic growth and cell division in metabolically permissive conditions may be directly connected to the shuttling of regulatory RNAs through EVs, which may relieve the intracellular control on the one side, and inhibit the adaptive effector response of EV target cells at the paracrine and endocrine level. The impairment of this mechanism in pwRR-MS may drive the design of novel treatments aimed at restoring immunological self-tolerance in autoimmunity.

About Paola de Candia
Dr. de Candia was born and raised in Napoli, Italy, and graduated in Biology in 1997 from the hometown University "Federico II." She obtained her PhD in Biochemistry in 2002, with research on tumor neo-angiogenesis in the laboratory of Dr. Robert Benezra at the Memorial Sloan Kettering Cancer Center in New York City. She then completed her postdoctoral training in human molecular evolution at the University of Chicago, USA. In 2008, Dr. de Candia returned to Italy with a fellowship at the Università di Milano Bicocca and subsequently joined the Istituto Nazionale Genetica Molecolare (INGM) in Milan. There, she began her independent research on human CD4+ T lymphocytes, focusing particularly on the physiological and pathological roles of extracellular vesicles in T cell-to-cell communication. In 2021, Dr. de Candia was appointed Professor of Biochemistry at the Università di Napoli "Federico II," where she continues to pursue her research interests in T cell biology.

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