Abstract

In this study, we investigated mechanisms by which regulatory B cells (Bregs) suppress CNS autoimmune diseases such as Uveitis or Multiple Sclerosis. These studies focused on Bregs that secrete IL-10, IL-27 or IL-35. We have isolated these Breg cells from human blood or bone marrow and in mice they were isolated from the spleen or peritoneal cavity. We are now characterizing the Breg cells transcriptomes by single-cell RNA-Seq (scRNA-Seq), Chip-Seq, ATAC-Seq. We have also isolated IL-35 containing exosomes from IL-35-producing Bregs (i35-Bregs), demonstrated that they suppress experimental autoimmune uveitis (EAU), suggesting that exosomes derived from Bregs can be exploited for adoptive immunotherapy in CNS autoimmune and neurodegenerative diseases.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAEY000262-24
Application #
10019976
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
24
Fiscal Year
2019
Total Cost
Indirect Cost

  Institution

Name
U.S. National Eye Institute
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Yu, Cheng-Rong; Choi, Jin Kyeong; Uche, Anita N et al. (2018) Production of IL-35 by Bregs is mediated through binding of BATF-IRF-4-IRF-8 complex to il12a and ebi3 promoter elements. J Leukoc Biol 104:1147-1157
Choi, Jin Kyeong; Dambuza, Ivy M; He, Chang et al. (2017) IL-12p35 Inhibits Neuroinflammation and Ameliorates Autoimmune Encephalomyelitis. Front Immunol 8:1258
Wang, Xiaoqian; Wei, Yinxiang; Xiao, He et al. (2016) Pre-existing CD19-independent GL7(-) Breg cells are expanded during inflammation and in mice with lupus-like disease. Mol Immunol 71:54-63
Wang, Xiaoqian; Wei, Yinxiang; Xiao, He et al. (2016) A novel IL-23p19/Ebi3 (IL-39) cytokine mediates inflammation in Lupus-like mice. Eur J Immunol 46:1343-50
Egwuagu, C E; Sun, L; Kim, S-H et al. (2015) Ocular Inflammatory Diseases: Molecular Pathogenesis and Immunotherapy. Curr Mol Med 15:517-28
Egwuagu, Charles E; Yu, Cheng-Rong; Sun, Lin et al. (2015) Interleukin 35: Critical regulator of immunity and lymphocyte-mediated diseases. Cytokine Growth Factor Rev 26:587-93
Egwuagu, Charles E; Yu, Cheng-Rong (2015) Interleukin 35-Producing B Cells (i35-Breg): A New Mediator of Regulatory B-Cell Functions in CNS Autoimmune Diseases. Crit Rev Immunol 35:49-57
Sun, Lin; He, Chang; Nair, Lekha et al. (2015) Interleukin 12 (IL-12) family cytokines: Role in immune pathogenesis and treatment of CNS autoimmune disease. Cytokine 75:249-55
Wang, Ren-Xi; Yu, Cheng-Rong; Dambuza, Ivy M et al. (2014) Interleukin-35 induces regulatory B cells that suppress autoimmune disease. Nat Med 20:633-41
Amadi-Obi, Ahjoku; Yu, Cheng-Rong; Dambuza, Ivy et al. (2012) Interleukin 27 induces the expression of complement factor H (CFH) in the retina. PLoS One 7:e45801

Showing the most recent 10 out of 13 publications