Our observations provide new insights about the MZ B cell translocation in lupus patients as well as the dichotomy of TLR9 and TLR7 signals in the pathogenesis of lupus.
These findings suggest a unique link between neutrophils and B cells in which NETs trigger a concerted activation of TLR9 and BCR leading to anti-NET autoantibody production in lupus.
The ability of TLR9 to detect and elicit an immune response against double-stranded DNA makes TLR9 a relevant factor to be tested for its association with the clinical and serological phenotypes of lupus.
Hence, this study was carried out to analyze the G to A and C to T transitions in TLR2 and TLR9 genes respectively and to test their association with lupus susceptibility, clinical and autoantibody phenotypes in South Indian Tamils.
African American women with lupus had a 2-fold increase in TLR-9 expression level when compared to their healthy controls or European American lupus patients.
These results demonstrate that both TLR9 and TLR4 are required for 'full-blown' autoimmunity and organ injury in experimental lupus induced by pristane.
And the increase of the co-expression of TLR9 and T-bet may be of benefit to the protective antibodies' production and pathogenic antibodies' decline, and could be regarded as a good sign for lupus demission and/or treatment.
These results suggest that up-regulated expression of TLR7 and TLR9 mRNAs together with increased expression of IFN-alpha mRNA in PBMCs may also contribute to the pathogenesis of human lupus.
In this review, we discuss the rationale for self-recognition by TLR7 and TLR9 as an important part of the development of lupus and other autoimmune diseases.
Treatment of lupus-prone mice with a dual inhibitor of TLR7 and TLR9 leads to reduction of autoantibody production and amelioration of disease symptoms.