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. 2020 Apr 14;10:6405. doi: 10.1038/s41598-020-63042-3

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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IL-33 enhanced a regulatory and Th2 immune response through MC. (A) Immunofluorescence staining of LVV inflammatory lesions of 2 LVV patients and 1 non-inflammatory aorta control for ST2 and MC. (B) The number of MC within aorta was higher in LVV patients (n = 7) than in non-inflammatory controls (n = 3) *P < 0.05. These data are shown as the mean ± SEM. (C) Quantitative determination of Th2 cytokines in culture supernatants (n = 8) of MC and CD4⁺ T cells. IL-33-stimulated MC led to a significant increase in IL-5, IL-13 and IL-4 secretion. *P < 0.05, **P < 0.01. These data are shown as the mean ± SEM. (D) Left panel: Dot plots representing the proportion of CD25^highFOXP3⁺ and CD127^lowFOXP3⁺ CD4⁺ cells are shown. On the left: CD4⁺ T cells of one LVV patient are cultured for 5 days without IL-33. The proportion of CD127^lowFOXP3⁺ CD4⁺ cells is shown. On the middle: MC and stimulated CD4 T cells were cultured for 5 days without IL-33. On the right: MC and stimulated T CD4 cells were cultured for 5 days with IL-33. This patient is representative of the whole cohort (n = 8). Middle panel: The corresponding results of 8 LVV patients. MC alone and IL-33-stimulated MC promote the increase of Tregs frequency. *P < 0.05, **P < 0.01. These results are from 8 independent experiments. These data are shown as the mean ± SEM. Right panel: Quantitative determination of cytokines was performed in culture supernatants (n = 8). IL-33-stimulated MC led to a significant increase in IL-2 secretion. *P < 0.05, **P < 0.01. These data are shown as the mean ± SEM. (E) Left and middle panels: MC were incubated with LVV serum (n = 11) with or without IL-33 stimulation. IL-33 led to a discreet increase of MC degranulation (histamine and tryptase). Right panel: Indoleamine 2 3-dioxygenase (IDO) activity was dramatically increased in MC incubated with IL-33 as compared to those not stimulated with IL-33.**P < 0.01, ***P < 0.001. These data are shown as the mean ± SEM.