Abstract
Purpose :
Autoimmune uveitis (AU) is a sort of blinding ocular inflammatory disorders. Immunological inflammation has been regarded as the key of the pathogenesis in AU. Baicalin, the major component of S. baicalensis, possess immunomodulatory properties in several autoimmune diseases. However, the role of baicalin in uveitis and underlying mechanisms remains unclear. In this study, we investigate the therapeutic effects and mechanism of baicalin in experimental autoimmune uveitis (EAU).
Methods :
Different dosages of baicalin, or Vehicle were intraperitoneally injected daily with EAU mice from day 7 after hIRBP1–20 immunization (N=6). Clinical scores and pathological grades were evaluated on day 21. Retinas and draining lymph nodes (DLNs) were collected for the expression assessment of inflammatory cytokines. Cell suspensions of DLNs and spleens were achieved for the frequency and number of regulator T cell (Treg) and effector T cell (Teff, mainly Th1 and Th17). In vitro, DLN cells from EAU mice were cultured in hIRBP (15μg/ml) with baicalin treatment (0, 5, 10, 20 μg/ml), Treg and Teff was detected by flow cytometry assay.
The aryl hydrocarbon receptor (AhR) expression of IRBP-specific CD4+ T cell and EAU mice was detected by qPCR and Western Bolt after baicalin treatment. Next, an AhR inhibitor, CH223191, was then applied to IRBP-specific CD4+ T cell and EAU mice (N= 3) with/without baicalin treatment compared.
Results :
Baicalin treatment obviously inhibited the intraocular inflammatory process, along with obviously declines in the inflammatory cytokine transcription in the retinas and DLNs. Baicalin treatment increased the frequency and number of Treg, decreased the frequency and number of Th1 and Th17 in EAU mice. In vitro, baicalin treatment suppressed the IRBP-specific CD4+ T cell proliferation and converted CD4+ T cell differentiation. The expression of AhR obviously increased both in vitro and in vivo after baicalin treatment. The baicalin-mediated CD4+T cell differentiation was partly abrogated when the AhR inhibitor, CH223191, was used both in vivo and in vitro.
Conclusions :
Our results suggest that baicalin modulates Treg/Teff cell balance and CD4+T cell proliferation to ameliorate EAU by activating the AhR signaling. These findings bring compelling evidence that baicalin can protect against EAU and emerge as a promising candidate in the treatment of autoimmune diseases.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.