IADR Abstract Archives
DEL-1 Restrains Rheumatoid Arthritis By Downregulating T Follicular Helper Cells
Objectives: We have previously shown that the secreted protein DEL-1 (developmental endothelial locus-1) inhibits periodontal inflammation and bone loss. Here, our aim was to study whether DEL-1 can also inhibit another bone loss disorder that is epidemiologically associated with periodontitis. Specifically, we investigated whether and how DEL-1 can restrain rheumatoid arthritis (RA), a chronic autoimmune disease for which there are currently no effective host-modulation treatments.
Methods: Collagen-induced arthritis (CIA) and collagen antibody-induced arthritis (CAIA) models were employed to test the anti-arthritogenic effects of DEL-1 using mice with collagen VI-specific overexpression of DEL-1 (‘ColVI-Del1’ mice). DEL-1 expression levels were detected by in situ hybridization (RNAscope) and immunohistochemistry. Staining with hematoxylin and eosin or safranin-O was performed to detect tissue pathology. Immune responses were analyzed by flow cytometry and ELISA.
Results: Compared to wild-type (WT) littermate control mice, ColVI-Del1 mice displayed reduced severity of arthritis, as shown by significantly decreased inflammatory cell infiltration, synovial hyperplasia, and cartilage destruction. Importantly, in the inguinal lymph nodes, the frequencies and numbers of germinal center (GC) B cells and T follicular helper (Tfh) cells, as well as the serum levels of Type II collagen (CII)-specific IgG antibodies were significantly lower in ColVI-Del1 mice as compared to WT littermate controls. Moreover, DEL-1 was localized in the T-B cell border and T cell zone in inguinal lymph nodes. In contrast, there were no differences between ColVI-Del1 and WT littermate control mice in terms of disease severity in CAIA model, in which disease is induced by administration of premade arthritogenic antibodies.
Conclusions: DEL-1 appears to restrain RA by interfering with the induction of the arthritogenic antibodies, although additional studies are required to better understand the mechanisms involved. Together with our earlier findings, this study suggests that DEL-1 may be a promising therapeutic for the treatment of bone loss disorders including periodontitis and RA.
Methods: Collagen-induced arthritis (CIA) and collagen antibody-induced arthritis (CAIA) models were employed to test the anti-arthritogenic effects of DEL-1 using mice with collagen VI-specific overexpression of DEL-1 (‘ColVI-Del1’ mice). DEL-1 expression levels were detected by in situ hybridization (RNAscope) and immunohistochemistry. Staining with hematoxylin and eosin or safranin-O was performed to detect tissue pathology. Immune responses were analyzed by flow cytometry and ELISA.
Results: Compared to wild-type (WT) littermate control mice, ColVI-Del1 mice displayed reduced severity of arthritis, as shown by significantly decreased inflammatory cell infiltration, synovial hyperplasia, and cartilage destruction. Importantly, in the inguinal lymph nodes, the frequencies and numbers of germinal center (GC) B cells and T follicular helper (Tfh) cells, as well as the serum levels of Type II collagen (CII)-specific IgG antibodies were significantly lower in ColVI-Del1 mice as compared to WT littermate controls. Moreover, DEL-1 was localized in the T-B cell border and T cell zone in inguinal lymph nodes. In contrast, there were no differences between ColVI-Del1 and WT littermate control mice in terms of disease severity in CAIA model, in which disease is induced by administration of premade arthritogenic antibodies.
Conclusions: DEL-1 appears to restrain RA by interfering with the induction of the arthritogenic antibodies, although additional studies are required to better understand the mechanisms involved. Together with our earlier findings, this study suggests that DEL-1 may be a promising therapeutic for the treatment of bone loss disorders including periodontitis and RA.