Abstract
Background
We investigated a costimulatory molecule OX40–OX40L acting as an upstream regulator to regulate the nuclear factor of activated T cell (NFAT) in the acute phase of Kawasaki disease (KD).
Methods
One hundred and one samples were collected and divided into six groups: coronary artery lesion (KD-CAL) before intravenous immunoglobulin (IVIG), KD-CAL after IVIG, KD without CAL (KD-nCAL) before IVIG, KD-nCAL after IVIG, fever of unknown (Fou), and Healthy. In vitro OX40-stimulating and OX40L-inhibiting tests were conducted in Healthy and KD groups, respectively. Both the messenger RNA (mRNA) and protein expression levels of OX40, OX40L, NFAT1, and NFAT2 were investigated using quantitative reverse transcription PCR and immunoblotting assay, respectively.
Results
The mRNA and protein expression levels of NFAT1, NFAT2, OX40, and OX40L were significantly increased in KD-CAL and KD-nCAL groups before IVIG compared with Fou and Healthy groups and decreased after IVIG. A positive correlation was found between them in KD. In vitro OX40-stimulating test demonstrated the significantly increased mRNA and protein expression levels of NFAT1 and NFAT2 in the peripheral blood mononuclear cells of the Healthy group. Meanwhile, OX40L-inhibiting test showed significantly decreased expression levels of NFAT1 and NFAT2 in the KD group.
Conclusion
OX40–OX40L acts as an upstream regulator in the NFAT signaling pathway involved in KD.
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Acknowledgements
This work was supported by the grants from the National Natural Science Foundation of China (Nos. 81570455, 31600695, and 8187021691), the Natural Science Foundation of Young (Nos. 81600391, 81400222, 81570439, and 81800437), the Jiangsu Province Science Foundation (No. BE2017660), the Talent Foundation of Jiangsu Province (No. WSN-070 and ZDRCA2016049), the Jiangsu Provincial Medical Young Talents (QNRC2016756 and QNRC2016764), the Universities Natural Science Foundation of Jiangsu Province (16KJB310014), and the Applied Foundational Research of Medical and Health Care of Suzhou City (SYS201642 and SYS201633).
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Y.-W.L. carried out the studies and wrote the paper and Y.C. participated in its design and wrote the paper. H.-T.L. helped to design the manuscript and wrote the paper. X.L., Y.-J.T., W.-G.Q., Q.-Q.X., and L.S. participated in the collection of clinical cases. G.-H.Q., as the co-corresponding author, participated in the experimental process. Y.-Y.D., as the first corresponding author, participated in the design of the whole study and wrote the manuscript. All authors read and approved the final manuscript.
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Lv, YW., Chen, Y., Lv, HT. et al. Kawasaki disease OX40–OX40L axis acts as an upstream regulator of NFAT signaling pathway. Pediatr Res 85, 835–840 (2019). https://doi.org/10.1038/s41390-019-0312-0
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DOI: https://doi.org/10.1038/s41390-019-0312-0
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