Background Neuropsychiatric SLE (NPSLE) is a common manifestation of SLE and problems such as cognitive impairment or depression are elusive. The importance of innate immune related inflammation in the pathomechanism of neurodegenerative or psychiatric diseases has been recognized recently, and the importance of innate immunity in the pathogenesis of NPSLE has also been suggested¹⁾. Therefore, we investigated innate immune mechanism of NPSLE by using lupus prone mice.

Objectives This study is conducted to understand the brain immune pathology of lupus-prone FcγRIIB^-/-Yaa mice in which innate immune stimulation is potentiated by the duplication of Toll-like receptor 7²⁾.

Methods Immune cell subsets and histopathology of brains were analyzed by flow cytometry and immunohistochemistry in FcγRIIB^-/-Yaa mice compared with congenic mice at around 16 week-old when glomerulonephritis had developed. For flow cytometric analysis, microglia, myeloid lineage cells and lymphocytes were defined by staining with CD11b and CD45. Subsets of those cells and their activation status were analyzed. For histopathological analysis, microglia, brain macrophages, astrocytes and lymphocytes were immunostained and expression of MHC class I and class II were also analyzed.

Results Flow cytometric analysis revealed increase in the number of microglial cells (CD11b⁺ CD45^int) and myeloid lineage cells (CD11b⁺ CD45^high) in the brains of FcγRIIB^-/-Yaa mice compared with congenic FcγRIIB^+/+ mice. Mean fluorescence intensity of MHC class I was increased in microglia and myeloid lineage cells in FcγRIIB^-/-Yaa mice. An increased percentage of CD3 positive cells compared to CD19 positive cells were observed and their expression of CD69, an activation marker, were increased in FcγRIIB^-/-Yaa mice. In histopathology, number of macrophages and microglia identified by Iba1 (Ionized calcium binding adapter molecule 1) positive cells were increased in FcγRIIB^-/-Yaa mice. In areas where MHC class I and class II were highly expressed on macrophages, reaction of astrocytes and patchy increase of lymphocytes were also observed. Furthermore, MHC class I and class II were also highly expressed in the vascular endothelium in FcγRIIB^-/-Yaa mice.

Conclusions Activation of myeloid lineage cells and reactive changes of glial cells and endothelial cells were observed in the central nervous system of lupus-prone FcγRIIB^-/-Yaa mice. These results imply the role of innate immune mechanisms in the pathology of NPSLE.

References

1. Stock AD, Wen J, Doerner J, et al. Neuropsychiatric systemic lupus erythematosus persists despite attenuation of systemic disease in MRL/lpr mice. J Neuroinflammation.2015;12:205.

2. Kawano S, Lin Q, Amano H, et al. Phenotype conversion from rheumatoid arthritis to systemic lupus erythematosus by introduction of Yaa mutation into FcγRIIB-deficient C57BL/6 mice. Eur J Immunol.2013;43:770–8.

References

Disclosure of Interest None declared