Purpose
Experimental autoimmune uveitis (EAU), a T cell-mediated model of uveitis in mice, is dependent on the use of Freund’s adjuvant containing killed M. tuberculosis. Toll-like receptors (TLRs) such as TLR4 are crucial for the recognition of the adjuvant by the innate immune system. Endogenous TLR ligands might positively or negatively modulate this process. We examined whether or not the endogenous TLR4 ligand S100A9 plays a role in EAU.
Methods
We induced EAU in S100A9 -/- mice on a C57BL/6 background and C57BL/6 wild type mice through subcutaneous injection of interphotoreceptor retinoid-binding protein (IRBP) peptide 1-20 emulsified in complete Freund’s adjuvant augmented with intraperitoneal pertussis toxin. EAU severity was monitored by weekly clinical exam using a 90 diopter lens and indirect ophthalmoscope. Histological grading was performed at the conclusion of the experiment.
Results
S100A9 -/- mice showed increased EAU severity as indicated by clinical exam on days 13 and 20 post-IRBP immunization but this difference was not statistically significant at days 28-48. On day 20, 72.7% of S100A9 -/- mice received clinical scores ≥1 compared to 20.0% of wild type mice (Fig. 2A, p=0.020). Consistent with the clinical grading on days 35-48, on which there was no difference in clinical score, there was no difference seen in histological grading between S100A9 -/- and wildtype (Fig. 2B, 40.0% compared to 42.90%, p=0.889).
Conclusions
The endogenous toll ligand S100A9 may be important at certain phases of EAU, as its absence surprisingly resulted in increased disease, similar to our previous findings with the endotoxin-induced uveitis (EIU) model.
Keywords: 746 uveitis-clinical/animal model •
555 immunomodulation/immunoregulation •
557 inflammation