Purchase this article with an account.
Tomas Blanco, Hayate Nakagawa, Hamid Alemi, Rohan Bir Singh, shuyan zhu, Yukako Taketani, Sonia Anchouche, Yihe Chen, Sunil Chauhan, Jia Yin, Reza Dana; CD103+ Dendritic Cells Suppress Th1 Alloimmunity by Modulating CD11b+ Antigen Presenting Cells via IL-10. Invest. Ophthalmol. Vis. Sci. 2021;62(8):879.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Conventional dendritic cells (cDC) are critical for initiating T helper-1(Th1) alloimmunity post-corneal transplantation; however, the differential roles and molecular mechanisms of migratory CD103+ cDC and CD11b+ Ag-presenting cells (APC) subsets in Th1 alloimmunity have not been completely investigated. Herein, we examined the function of CD103+ DC in regulating CD11b+ APC-mediated anti-allograft Th1 immunity
High risk (HR) and low risk (LR) allogeneic corneal transplantation were performed using C57BL/6 mice as donors and BALB/c as hosts. On days 1,3,4,7,and 14 post-transplantation, CD103+CD11c+ DC, B220-CD11b+MHC-IIhigh APC, CD4+CD25+FoxP3+ regulatory T cells (Treg), and CD4+IFN-g+ (Th1) cells, were assessed by flow cytometry in graft recipient mice. On day 14, CD103+ DC of LR graft recipients and CD11b+ APC of HR graft recipients were FACS-sorted, incubated, and assessed for production of IL-10 and IL-12 by ELISA. CD11b+ APC were co-cultured with syngeneic CD103+ DC, syngeneic and CD4+CD25- T cells, and allogeneic corneal lysate. Anti-IL10R blocking antibody was added, and IL-12 and IFN-g were measured by ELISA in supernatants
CD103+ DC frequencies were significantly higher in LR setting compared to HR (p<0.001). CD11b+MHC-IIhigh APC frequencies were found significantly augmented in the HR setting compared to LR (p<0.001). Funtional Treg (measured by FoxP3 expression) were found significantly higher in LR vs. HR (p<0.01), but no significant change in Treg-frequencies was observed. Th1 cell frequencies were significantly increased in HR vs. LR (p<0.001). IL-10 production was significantly reduced (p<0.001) and IL-12 significantly increased (p<0.001) by CD11b+ APC compared to CD103+ DC. The presence of CD103+ DC with CD11b APC led to a significant reduction in IL-12 secretion by CD11b+ APC (p<0.001) and modulation of allosensitization measured by IFN-g production by Th1 cells compared to CD11b+ DC alone (p<0.001). Blocking IL-10R, abrogated the modulatory effect of CD103+ DC on CD11b+ APC
These results provide novel insights into the distinct roles of migratory DC subsets in the regulation of Th1 immunity. Additionally, they show that CD103+ DC are critical for regulating Th1 immunity following corneal transplantation
This is a 2021 ARVO Annual Meeting abstract.
This PDF is available to Subscribers Only