Abstract
The peptidylarginine deiminases (PADs) and the citrullinated proteins that they generate have key roles in innate immunity and rheumatoid arthritis, an inflammatory arthritis with antibodies that target citrullinated proteins. However, the importance of PADs, particularly PAD2, in the adaptive immune response, both normal and pathogenic, is newly emerging. In this study, we evaluated a requirement for PAD2 in the antibody response in collagen-induced arthritis (CIA), a T and B cell-driven murine model of rheumatoid arthritis, and in the protective antibody response to murine influenza infection. Using PAD2−/− and PAD2+/+ mice on the DBA/1J background, we found that PAD2 is required for maximal anti-collagen antibody levels, but not collagen-specific plasma cell numbers, T cell activation or polarization, or arthritis severity in CIA. Also, we found that PAD2 is required not just for normal levels of persistent hemagglutination inhibiting antibodies but also for full protection from lethal influenza rechallenge. Together, these data provide evidence for a novel modest requirement for PAD2 in a normal antiviral antibody response and in an abnormal autoantibody response in inflammatory arthritis.
Highlights
The peptidylarginine deiminases (PADs) are essential components of normal and pathologic inflammation
Since IgG levels were reduced in the absence of PAD2 in TNF-induced arthritis [5], we evaluated a requirement for PAD2 in anti-collagen IgG levels by Enzyme-Linked Immunosorbent Assay (ELISA)
Given the role of PAD2 in IL-17 production, we evaluated a requirement for PAD2 in the T cell compartment in collagen-induced arthritis (CIA)
Summary
The peptidylarginine deiminases (PADs) are essential components of normal and pathologic inflammation. They catalyze citrullination, the posttranslational modification of arginine to the nonstandard amino acid citrulline. More recent work demonstrates a requirement for the PADs in adaptive immune responses, and PAD2 appears to play a prominent role. It is required for production of IL-17A, but not IFNγ, by T cells from imiquimod-treated, but not untreated, mice [8] with a similar requirement for PAD2 in IL-17A production by in vitro differentiated Th17 cells [3]. PAD2 is required to suppress IL-4 production by Th2differentiated T cells, but has no effect on IFNγ production by Th1-differentiated cells [3]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
