@article{bcb44caab1874b518774a7afa3a93363,
title = "Cbl-b restrains priming of pathogenic Th17 cells via the inhibition of IL-6 production by macrophages",
abstract = "E3 ubiquitin ligase Cbl-b is involved in the maintenance of a balance between immunity and tolerance. Mice lacking Cbl-b are highly susceptible to experimental autoimmune encephalomyelitis (EAE), a Th17-mediated autoimmune disease. However, how Cbl-b regulates Th17 cell responses remains unclear. In this study, utilizing adoptive transfer and cell type-specific Cblb knockout strains, we show that Cbl-b expression in macrophages, but not T cells or dendritic cells (DCs), restrains the generation of pathogenic Th17 cells and the development of EAE. Cbl-b inhibits IL-6 production by macrophages that is induced by signaling from CARD9-dependent C-type lectin receptor (CLR) pathways, which directs T cells to generate pathogenic Th17 cells. Therefore, our data unveil a previously unappreciated function for Cbl-b in the regulation of pathogenic Th17 responses.",
keywords = "Biological sciences, Immune response, Immunology",
author = "Qiuming Zeng and Na Tang and Yilei Ma and Hui Guo and Yixia Zhao and Rong Tang and Chengkai Yan and Song Ouyang and Langdon, {Wallace Y.} and Huan Yang and O'Brien, {Matthew C.} and Jian Zhang",
note = "Funding Information: We thank Drs. Josef M. Penninger, Gordon D. Brown and Yoichiro Iwakura for providing Cblb−/−, Clec7a−/− and Clec4n−/− mice. This work was supported by the US National Institutes of Health (R01 AI090901, R01 AI121196, and R01 AI123253 to J.Z.). Q.Z. was supported by a Scholarship from the China Scholarship Council (CSC). J.Z. is a University of Iowa Health Care Distinguished Scholar. Q.Z. and N.T. performed most in vitro and in vivo experiments, and analyzed the data; and Y.M. H.G. M.C.B. C.Y. R.T. Y.Z. and S.O. performed some in vitro and in vivo experiments; W.Y.L. and H.Y. helped with the design of the experiments, and edited the manuscript; J.Z. conceived and planned the research, and analyzed the data; and Q.Z. N.T. and J.Z. wrote the manuscript. The authors declare no competing financial interests. We worked to ensure sex balance in the selection of non-human subjects. We worked to ensure diversity in experimental samples through the selection of the cell lines. While citing references scientifically relevant for this work, we also actively worked to promote gender balance in our reference list. Funding Information: We thank Drs. Josef M. Penninger, Gordon D. Brown and Yoichiro Iwakura for providing Cblb −/− , Clec7a −/− and Clec4n −/− mice. This work was supported by the US National Institutes of Health ( R01 AI090901 , R01 AI121196 , and R01 AI123253 to J.Z.). Q.Z. was supported by a Scholarship from the China Scholarship Council (CSC). J.Z. is a University of Iowa Health Care Distinguished Scholar. Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = oct,
day = "21",
doi = "10.1016/j.isci.2022.105151",
language = "English",
volume = "25",
journal = "Iscience",
issn = "2589-0042",
publisher = "Cell Press",
number = "10",
}