Abstract
Regulatory B cells (Bregs) that produce IL-35 and IL-10 (i35-Bregs) regulate central nervous system (CNS) autoimmune diseases including uveitis. In the mouse model of uveitis, i35-Breg cells suppress intraocular inflammation by inducing expansion of IL-10-producing B cells (B10), IL-10-producing T cells (Tregs), and IL-35-producing T cells (iTR35), suggesting that i35-Bregs orchestrate an immune-suppressive milieu that regulates immunity during autoimmune diseases. In this chapter, we discuss uveitis and therapeutic challenges that necessitate the development of cell-based therapies for the treatment of these potentially blinding diseases that cause 10% visual handicap. We then describe the methods we set up for ex vivo generation of i35-Breg cells employed in i35-Breg immunotherapy in uveitis and in other CNS autoimmune diseases.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Nussenblatt RB (1990) The natural history of uveitis. Int Ophthalmol 14(5–6):303–308
Nussenblatt RB (1991) Proctor lecture. Experimental autoimmune uveitis: mechanisms of disease and clinical therapeutic indications. Invest Ophthalmol Vis Sci 32(13):3131–3141
Wraith DC, Nicholson LB (2012) The adaptive immune system in diseases of the central nervous system. J Clin Invest 122(4):1172–1179
Streilein JW (2003) Ocular immune privilege: therapeutic opportunities from an experiment of nature. Nat Rev Immunol 3(11):879–889
Caspi RR (2010) A look at autoimmunity and inflammation in the eye. J Clin Invest 120(9):3073–3083
Vignali DA, Kuchroo VK (2012) IL-12 family cytokines: immunological playmakers. Nat Immunol 13(8):722–728
Fitzgerald DC, Ciric B, Touil T, Harle H, Grammatikopolou J, Das Sarma J, Gran B, Zhang GX, Rostami A (2007) Suppressive effect of IL-27 on encephalitogenic Th17 cells and the effector phase of experimental autoimmune encephalomyelitis. J Immunol 179(5):3268–3275
Shen P, Roch T, Lampropoulou V, O'Connor RA, Stervbo U, Hilgenberg E, Ries S, Dang VD, Jaimes Y, Daridon C, Li R, Jouneau L, Boudinot P, Wilantri S, Sakwa I, Miyazaki Y, Leech MD, McPherson RC, Wirtz S, Neurath M, Hoehlig K, Meinl E, Grutzkau A, Grun JR, Horn K, Kuhl AA, Dorner T, Bar-Or A, Kaufmann SH, Anderton SM, Fillatreau S (2014) IL-35-producing B cells are critical regulators of immunity during autoimmune and infectious diseases. Nature 507(7492):366–370
Zundler S, Neurath MF (2015) Interleukin-12: functional activities and implications for disease. Cytokine Growth Factor Rev 26(5):559–568
Wang X, Wei Y, Xiao H, Liu X, Zhang Y, Han G, Chen G, Hou C, Ma N, Shen B, Li Y, Egwuagu CE, Wang R (2016) A novel IL-23p19/Ebi3 (IL-39) cytokine mediates inflammation in lupus-like mice. Eur J Immunol 46(6):1343–1350
Amadi-Obi A, Yu CR, Liu X, Mahdi RM, Clarke GL, Nussenblatt RB, Gery I, Lee YS, Egwuagu CE (2007) T(H)17 cells contribute to uveitis and scleritis and are expanded by IL-2 and inhibited by IL-27/STAT1. Nat Med 13(6):711–718
Choi JK, Dambuza IM, He C, Yu CR, Uche AN, Mattapallil MJ, Caspi RR, Egwuagu CE (2017) IL-12p35 inhibits Neuroinflammation and ameliorates autoimmune encephalomyelitis. Front Immunol 8:1258
Dambuza IM, He C, Choi JK, Yu CR, Wang R, Mattapallil MJ, Wingfield PT, Caspi RR, Egwuagu CE (2017) IL-12p35 induces expansion of IL-10 and IL-35-expressing regulatory B cells and ameliorates autoimmune disease. Nat Commun 8(1):719
Wang RX, Yu CR, Dambuza IM, Mahdi RM, Dolinska MB, Sergeev YV, Wingfield PT, Kim SH, Egwuagu CE (2014) Interleukin-35 induces regulatory B cells that suppress autoimmune disease. Nat Med 20(6):633–641
Mattapallil MJ, Wawrousek EF, Chan CC, Zhao H, Roychoudhury J, Ferguson TA, Caspi RR (2012) The Rd8 mutation of the Crb1 gene is present in vendor lines of C57BL/6N mice and embryonic stem cells, and confounds ocular induced mutant phenotypes. Invest Ophthalmol Vis Sci 53(6):2921–2927
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Choi, J.K., Egwuagu, C.E. (2021). Analysis of Regulatory B Cells in Experimental Autoimmune Uveitis. In: Mion, F., Tonon, S. (eds) Regulatory B Cells. Methods in Molecular Biology, vol 2270. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1237-8_23
Download citation
DOI: https://doi.org/10.1007/978-1-0716-1237-8_23
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-0716-1236-1
Online ISBN: 978-1-0716-1237-8
eBook Packages: Springer Protocols