ArticleCell death and differentiation2022
Progranulin regulates the development and function of NKT2 cells through EZH2 and PLZF.
Article in Cell death and differentiation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 12 citations in OpenAlex.
- The Major Role of Type 2 Inflammation in Asthma: From the Perspective of Immunological Mechanism.BioMed research international · 2026Review
- Exploring putative links between gut microbiota and allergic rhinitis: insights from Mendelian randomization and multi-transcriptome integration.AMB Express · 2025Article
- Decoding innate lymphoid cells and innate-like lymphocytes in asthma: pathways to mechanisms and therapies.Journal of biomedical science · 2025Review
- Mechanisms and Therapeutic Implications of EZH2 in Nasal Diseases.Clinical reviews in allergy & immunology · 2025Review
- The Emerging Roles and Therapeutic Potential of Unconventional T Cells in Sepsis.Journal of inflammation research · 2025Review
- SHIP-1 regulates the differentiation and function of Tregs via inhibiting mTORC1 activity.Cellular and molecular life sciences : CMLS · 2024Article
- PGRN Inhibits Early B-cell Activation and IgE Production Through the IFITM3-STAT1 Signaling Pathway in Asthma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T helper 2 (Th2) cytokine production by invariant natural killer T (iNKT) cells is involved in the development of asthma, but the regulation of Th2 cytokines in iNKT cells remains unknown. Although it is known that progranulin (PGRN) induces the production of Th2 cytokines in iNKT cells in vivo, the underlying mechanism is not clear. This study aims to investigate the role of PGRN in iNKT cells. The effects of PGRN on the differentiation of iNKT cells was detected by flow cytometry. Then stimulation of iNKT cells and airway resistance were carried out to evaluate the function of PGRN on iNKT cells. Furthermore, the mechanisms of PGRN in regulating iNKT cells was investigated by RT-PCR, WB, confocal and luciferase reporter assays. The absolute number of iNKT cells decreased in PGRN KO mice despite an increase in the percentage of iNKT cells. Furthermore, analyzing the subsets of iNKT cells, we found that NKT2 cells and their IL-4 production were reduced. Mechanistically, the decrease in NKT2 cells in the PGRN KO mice was caused by increased expression of enhancer of zeste homolog 2 (EZH2), that in turn caused increased degradation and altered nuclear localization of PLZF. Interestingly, PGRN signaling decreased expression of EZH2 and treatment of the PGRN KO mice with the EZH2 specific inhibitor GSK343 rescued the defect in NKT2 differentiation, IL-4 generation, and PLZF expression. Altogether, We have revealed a new pathway (PGRN-EZH2-PLZF), which regulates the Th2 responses of iNKT cells and provides a potentially new target for asthma treatment.
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