Ablation of interaction between IL-33 and ST2+ regulatory T cells increases immune cell-mediated hepatitis and activated NK cell liver infiltration

The IL-33/ST2 axis plays a protective role in T-cell-mediated hepatitis, but little is known about the functional impact of endogenous IL-33 on liver immunopathology. We used IL-33-deficient mice to investigate the functional effect of endogenous IL-33 in concanavalin A (Con A)-hepatitis. IL-33^–/– mice displayed more severe Con A liver injury than wild-type (WT) mice, consistent with a hepatoprotective effect of IL-33. The more severe hepatic injury in IL-33^–/– mice was associated with significantly higher levels of TNF-α and IL-1β and a larger number of NK cells infiltrating the liver. The expression of Th2 cytokines (IL-4, IL-10) and IL-17 was not significantly varied between WT and IL-33^–/– mice following Con A-hepatitis. The percentage of CD25⁺ NK cells was significantly higher in the livers of IL-33^–/– mice than in WT mice in association with upregulated expression of CXCR3 in the liver. Regulatory T cells (Treg cells) strongly infiltrated the liver in both WT and IL-33^–/– mice, but Con A treatment increased their membrane expression of ST2 and CD25 only in WT mice. In vitro, IL-33 had a significant survival effect, increasing the total number of splenocytes, including B cells, CD4⁺ and CD8⁺ T cells, and the frequency of ST2⁺ Treg cells. In conclusion, IL-33 acts as a potent immune modulator protecting the liver through activation of ST2⁺ Treg cells and control of NK cells.

From: Noel, G., Arshad, M. I., Filliol, A., Genet, V., Rauch, M., Lucas-Clerc, C., Lehuen, A., Girard, J.-P., Piquet-Pellorce, C., Samson, M. http://redirect.viglink.com?u=http%3A%2F%2Fajpgi.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F311%2F2%2FG313%3Frss%3D1&key=ddaed8f51db7bb1330a6f6de768a69b8