Plain-language summary
Eosinophilic chronic rhinosinusitis (ECRS) is a stubborn subtype of sinus inflammation driven by type 2 immune responses, and it often comes back after surgery. Because today's biological drugs help only some patients, researchers in Shanghai asked whether a cell-free alternative — small extracellular vesicles released by mesenchymal stem cells (MSC-sEV) — could calm the disease. Working with a papain-induced mouse model of ECRS, they delivered MSC-sEV through the nose during the challenge phase. Treated animals showed fewer symptoms and less tissue damage: a thinner lining, fewer mucus-producing goblet cells, less mucus and fewer eosinophils in the nasal mucosa. Tissue staining indicated reduced airway remodeling and a partial recovery of E-cadherin, a protein that helps epithelial cells stay tightly joined. In the spleen, flow cytometry showed a partial rebalancing of the disturbed Th1/Th2/Th17 landscape, with the strongest effect on the Th17 arm. Transcriptomics linked these changes to lower levels of chemokines that recruit eosinophils and to reduced IL-17, TNF and JAK-STAT signaling, which the team confirmed at the protein level. The study positions MSC-sEV as a promising cell-free approach for this difficult condition.
Key findings
- Intranasal MSC-derived small extracellular vesicles eased symptoms and tissue changes in a mouse model of eosinophilic chronic rhinosinusitis.
- Treated animals showed less epithelial thickening, fewer mucus-producing goblet cells, reduced mucus and fewer eosinophils in the nasal mucosa.
- The vesicles partially restored the disturbed Th1/Th2/Th17 balance, with the clearest effect on the Th17-related response.
- Transcriptomic and protein analyses pointed to lower eosinophil-recruiting chemokines and reduced IL-17, TNF and JAK-STAT signaling.
Original abstract
Eosinophilic chronic rhinosinusitis (ECRS) is a refractory subtype characterized by dominant Th2 inflammation and progressive tissue remodeling, with high postoperative recurrence and limited efficacy of current biological agents. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEV) represent a promising cell-free nanotherapeutic approach, yet their efficacy in ECRS remains poorly studied. This study investigated the therapeutic efficacy of intranasal MSC-sEV against Th2/Th17 immune dysregulation and mucosal remodeling in a papain-induced ECRS model. Intranasal administration of MSC-sEV during the challenge phase significantly alleviated clinical symptoms and attenuated key pathological features, including epithelial hyperplasia, goblet cell hyperplasia, excessive mucus secretion and mucosal eosinophil infiltration, the latter confirmed by direct eosinophil quantification on H&E-stained sections. Immunohistochemistry showed that MSC-sEV attenuated airway remodeling by downregulating markers such as FXIII-A and CLCA1 while partially restoring E-cadherin levels, indicating attenuation of EMT-like changes. Flow cytometry of splenic lymphocytes revealed that MSC-sEV partially restored the disturbed systemic Th1/Th2/Th17 balance, with a more evident effect on the Th17-associated response, and immunohistochemistry for GATA3, IL-17 A and TNF-α confirmed concordant changes in the nasal mucosa. Transcriptomic analysis showed that these therapeutic effects were associated with downregulation of eosinophil-recruitment chemokines (Ccl11, Ccl24) and with reduced enrichment of IL-17, TNF and JAK-STAT signaling-corroborated at the protein level by decreased phosphorylation of STAT3 and NF-κB p65 and by RT-qPCR confirmation of nine key transcripts. Collectively, this study identifies MSC-sEV as an effective cell-free strategy that attenuates the development of ECRS by partially restoring immune homeostasis and attenuating epithelial remodeling.
Frequently asked questions
What did this study find?
Eosinophilic chronic rhinosinusitis (ECRS) is a stubborn subtype of sinus inflammation driven by type 2 immune responses, and it often comes back after surgery. Because today's biological drugs help only some patients, researchers in Shanghai asked whether a cell-free alternative — small extracellular vesicles released by mesenchymal stem cells (MSC-sEV) — could calm the disease. Working with a papain-induced mouse model of ECRS, they delivered MSC-sEV through the nose during the challenge phase. Treated animals showed fewer symptoms and less tissue damage: a thinner lining, fewer mucus-producing goblet cells, less mucus and fewer eosinophils in the nasal mucosa. Tissue staining indicated reduced airway remodeling and a partial recovery of E-cadherin, a protein that helps epithelial cells stay tightly joined. In the spleen, flow cytometry showed a partial rebalancing of the disturbed Th1/Th2/Th17 landscape, with the strongest effect on the Th17 arm. Transcriptomics linked these changes to lower levels of chemokines that recruit eosinophils and to reduced IL-17, TNF and JAK-STAT signaling, which the team confirmed at the protein level. The study positions MSC-sEV as a promising cell-free approach for this difficult condition.
Was this tested in humans or in the laboratory?
This is delivery-science work, focused on how the vesicles behave when they are administered.
Where can I read the original paper?
The full text lives with the publisher: https://doi.org/10.1016/j.intimp.2026.117511
How to cite this paper
Cai Boyu, Wang Zhao, Xu Maoxiang, Li Jiaojiao, Li Danni, Tan Fei. Mesenchymal stem cell-derived small extracellular vesicles rebalance Th2/Th17 responses and attenuate epithelial remodeling in eosinophilic chronic rhinosinusitis.. International immunopharmacology. 2026, 2026-10-08. DOI: 10.1016/j.intimp.2026.117511
Source & verification
- Journal: International immunopharmacology
- Published: 8 October 2026
- DOI: 10.1016/j.intimp.2026.117511
- PubMed ID: 42849120
- Indexed via: pubmed
- MeSH terms: —