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ResearchIn-Press PreviewCardiology Open Access | 10.1172/JCI179262

Long non-coding RNA BCYRN1 promotes cardioprotection by enhancing human and murine regulatory T cell dynamics

Ke Liao,1 Jiayi Yu,1 Akbarshakh Akhmerov,1 Zahra Mohammadigoldar,1 Liang Li,1 Weixin Liu,1 Natasha Anders,1 Ahmed G.E. Ibrahim,1 and Eduardo Marbán1

1Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, United States of America

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1Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, United States of America

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1Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, United States of America

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1Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, United States of America

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1Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, United States of America

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1Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, United States of America

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1Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, United States of America

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1Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, United States of America

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1Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, United States of America

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Published March 25, 2025 - More info

J Clin Invest. https://doi.org/10.1172/JCI179262.
Copyright © 2025, Liao et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published March 25, 2025 - Version history
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Abstract

Regulatory T (Treg) cells modulate immune responses and attenuate inflammation. Extracellular vesicles from human cardiosphere-derived cells (CDC-EVs) enhance Treg proliferation and IL10 production, but the mechanisms remain unclear. Here we focus on BCYRN1, a long noncoding RNA (lncRNA) highly abundant in CDC-EVs, and its role in Treg cell function. BCYRN1 acts as a "microRNA sponge," inhibiting miR-138, miR-150, and miR-98. Suppression of these miRs leads to increased Treg cell proliferation via ATG7-dependent autophagy, CCR6-dependent Treg migration, and enhanced Treg IL10 production. In a mouse model of myocardial infarction, CDC-EVs, particularly those overexpressing BCYRN1, were cardioprotective, reducing infarct size and troponin I levels even when administered after reperfusion. Underlying the cardioprotection, we verified that CDC-EVs overexpressing BCYRN1 increased cardiac Treg infiltration, proliferation, and IL10 production in vivo. These salutary effects were negated when BCYRN1 levels were reduced in CDC-EVs, or when Tregs were depleted systemically. Thus, we have identified BCYRN1 as a booster of Treg number and bioactivity, rationalizing its cardioprotective efficacy. While here we studied BCYRN1 overexpression in the context of ischemic injury, the same approach merits testing in other disease processes (e.g., autoimmunity or transplant rejection) where increased Treg activity is a recognized therapeutic goal.

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