ArticleEBioMedicine2021
D-dopachrome tautomerase contributes to lung epithelial repair via atypical chemokine receptor 3-dependent Akt signaling.
Article in EBioMedicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 44 citations in OpenAlex.
- Preclinical models of COPD: a state of the art review.The European respiratory journal · 2026Review
- Lung organoids as a human system for Mycobacteria infection modeling and drug testing.The FEBS journal · 2026Review
- The multifaced role of the macrophage migration inhibitory factor family in organ fibrosis.American journal of physiology. Cell physiology · 2025Review
- Review
- An atypical atherogenic chemokine that promotes advanced atherosclerosis and hepatic lipogenesis.Nature communications · 2025Article
- Lung organoids in COPD: recent advances and future prospects.Respiratory research · 2025Review
- Revealing molecular and cellular heterogeneity in hypopharyngeal carcinogenesis through single-cell RNA and TCR/BCR sequencing.Frontiers in immunology · 2024Article
- The Role of Macrophage Migration Inhibitory Factor (MIF) and D-Dopachrome Tautomerase (D-DT/MIF-2) in Infections: A Clinical Perspective.Biomedicines · 2023Review
- Review
- CircRNA_0026344 via miR-21 is involved in cigarette smoke-induced autophagy and apoptosis of alveolar epithelial cells in emphysema.Cell biology and toxicology · 2023Article
- NanoBCell reports methods · 2023Article
- Hallmarks of Cancer Affected by the MIF Cytokine Family.Cancers · 2023Review
- CXCL12-CXCR4/CXCR7 Axis in Cancer: from Mechanisms to Clinical Applications.International journal of biological sciences · 2023Review
- CXCL14 promotes metastasis of non-small cell lung cancer through ACKR2-depended signaling pathway.International journal of biological sciences · 2023Article
- Atypical chemokine receptor 3 induces colorectal tumorigenesis in mice by promoting β-arrestin-NOLC1-fibrillarin-dependent rRNA biogenesis.Acta pharmacologica Sinica · 2022Article
- Modulatory role of macrophage migration inhibitory factor on cytokines and clinical features of sarcoidosis.Scientific reports · 2022Article
- Thieno[2,3-Journal of medicinal chemistry · 2022Article
- Macrophage migration inhibitory factor family proteins are multitasking cytokines in tissue injury.Cellular and molecular life sciences : CMLS · 2022Review
- 4-Iodopyrimidine Labeling Reveals Nuclear Translocation and Nuclease Activity for Both MIF and MIF2.Chemistry (Weinheim an der Bergstrasse, Germany) · 2022Article
- MIF but not MIF-2 recruits inflammatory macrophages in an experimental polymicrobial sepsis model.The Journal of clinical investigation · 2021Article
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEmphysematous COPD is characterized by aberrant alveolar repair. Macrophage migration inhibitory factor (MIF) contributes to alveolar repair, but for its structural and functional homolog D-dopachrome tautomerase (DDT) this is unknown. MIF mediates its effects through CD74 and/or C-X-C chemokine receptors 2 (CXCR2), 4(CXCR4), and possibly 7 (ACKR3). DDT can also signal through CD74, but interactions with other receptors have not been described yet. We therefore aimed at investigating if and how DDT contributes to epithelial repair in COPD.
methodsWe studied effects of recombinant DDT on cell proliferation and survival by clonogenic assay and annexin V-PI staining respectively. DDT-induced signaling was investigated by Western blot. Effects on epithelial growth and differentiation was studied using lung organoid cultures with primary murine or human epithelial cells and incubating with DDT or an ACKR3-blocking nanobody. DDT-ACKR3 interactions were identified by ELISA and co-immunoprecipitation.
findingsWe found that DDT promoted proliferation of and prevented staurosporine-induced apoptosis in A549 lung epithelial cells. Importantly, DDT also stimulated growth of primary alveolar epithelial cells as DDT treatment resulted in significantly more and larger murine and human alveolar organoids compared to untreated controls. The anti-apoptotic effect of DDT and DDT-induced organoid growth were inhibited in the presence of an ACKR3-blocking nanobody. Furthermore, ELISA assay and co-immunoprecipitation suggested DDT complexes with ACKR3. DDT could activate the PI3K-Akt pathway and this activation was enhanced in ACKR3-overexpressing cells.
interpretationIn conclusion, DDT contributes to alveolar epithelial repair via ACKR3 and may thus augment lung epithelial repair in COPD.
fundingAs stated in the Acknowledgments.
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