# Circ‐Eif3c Carried by M2 Macrophage‐Derived Exosomes Mitigates Asthma Progression via miR‐15a‐5p/GSS/SOCS6 Axis Inhibition

## TL;DR

This study shows that exosomes from M2 macrophages, which contain a specific circular RNA called circ-Eif3c, can reduce asthma symptoms by inhibiting inflammation and lung damage.

## Contribution

The novel finding is that circ-Eif3c in M2 macrophage-derived exosomes mitigates asthma progression via the miR-15a-5p/GSS/SOCS6 axis.

## Key findings

- M2Φ-Exos reduced OVA-induced inflammation and lung injury in mice.
- circ-Eif3c was upregulated in M2Φ-Exos and its downregulation reduced therapeutic effects.
- circ-Eif3c regulates miR-15a-5p, GSS, and SOCS6, and its overexpression enhanced M2Φ-Exos' protective effects.

## Abstract

In the study, we aimed to uncover potential therapeutic mechanisms concerning M2 macrophage‐derived exosomes in asthma.

Exosomes were isolated from M0Φ‐Exos and M2Φ‐Exos. An ovalbumin (OVA)‐induced asthma mouse model or lipopolysaccharide (LPS)‐induced alveolar epithelial cells (AECs) were created to unravel the therapeutic mechanisms. High‐throughput sequencing was used to search for differentially expressed circRNA. Bioinformation analysis and luciferase report analysis were used to reveal the regulationship among circ‐Eif3c, miR‐15a‐5p, glutathione synthetase (GSS), and suppressor of cytokine signaling 6 (SOCS6).

The results showed that M2Φ‐Exos suppressed OVA‐induced inflammatory cytokine secretion and lung injury in mice. Next‐generation sequencing (NGS) showed that circ‐Eif3c was upregulated in M2Φ‐Exos. Circ‐Eif3c downregulation inhibited the therapeutic effect of M2Φ‐Exos. Bioinformation analysis confirmed that miR‐15a‐5p, GSS, and SOCS6 were the downstream targets of circ‐Eif3c, which were confirmed by luciferase report analysis. The overexpression of miR‐15a‐5p or the downregulation of GSS/SOCS6 reversed circ‐Eif3c’s protective effects on LPS‐induced AEC damage. The overexpression of circ‐Eif3c increased the therapeutic effect of M2Φ‐Exos.

In conclusion, circ‐Eif3c‐enriched M2Φ‐Exos attenuated airway remodeling by restoring the function of AECs.