Fcgr2b and Fcgr3 are the major genetic factors for cartilage antibody-induced arthritis, overriding the effect of Hc encoding complement C5.

Like rheumatoid arthritis (RA) in humans, collagen-induced arthritis (CIA) in mice is associated with not only MHC class II genetic polymorphism but also, to some extent, with other loci including genes encoding Fc gamma receptors (FCGRs) and complement C5. In this study, we used a cartilage antibody-induced arthritis (CAIA) model in which arthritis develops within a 12-h timeframe, to determine the relative importance of FCGRs and C5 (Hc). In CAIA, inhibiting or deleting FCGR3 substantially hindered arthritis development, underscoring the crucial role of this receptor. Blocking FCGR3 also reduced the levels of FCGR4, and vice versa. When employing an IgG1 arthritogenic cocktail that exclusively interacts with FCGR2B and FCGR3, joint inflammation was promptly initiated in Fcgr2b-- mice but not in Fcgr3-- mice, suggesting that FCGR3 is sufficient for CAIA development. Regarding complement activation, Fcgr2b++.Hc** mice with C5 mutated were fully resistant to CAIA, whereas Fcgr2b--.Hc** mice developed arthritis rapidly. We conclude that FCGR3 is essential and sufficient for CAIA development, particularly when induced by IgG1 antibodies. The human ortholog of mouse FCGR3, FCGR2A, may be associated with RA pathogenesis. FCGR2B deficiency allows for rapid arthritis progression and overrides the resistance conferred by C5 deficiency.

A subset of type-II collagen-binding antibodies prevents experimental arthritis by inhibiting FCGR3 signaling in neutrophils.

Rheumatoid arthritis (RA) involves several classes of pathogenic autoantibodies, some of which react with type-II collagen (COL2) in articular cartilage. We previously described a subset of COL2 antibodies targeting the F4 epitope (ERGLKGHRGFT) that could be regulatory. Here, using phage display, we developed recombinant antibodies against this epitope and examined the underlying mechanism of action. One of these antibodies, R69-4, protected against cartilage antibody- and collagen-induced arthritis in mice, but not autoimmune disease models independent of arthritogenic autoantibodies. R69-4 was further shown to cross-react with a large range of proteins within the inflamed synovial fluid, such as the complement protein C1q. Complexed R69-4 inhibited neutrophil FCGR3 signaling, thereby impairing downstream IL-1ß secretion and neutrophil self-orchestrated recruitment. Likewise, human isotypes of R69-4 protected against arthritis with comparable efficiency. We conclude that R69-4 abrogates autoantibody-mediated arthritis mainly by hindering FCGR3 signaling, highlighting its potential clinical utility in acute RA.

3D hole-transporting materials based on coplanar quinolizino acridine for highly efficient perovskite solar cells.

Over the past five years, perovskite solar cells (PSCs) have gained intense worldwide attention in the photovoltaic community due to their low cost and high power conversion efficiencies (PCEs). One of the most significant issues in achieving high PCEs of PSCs is the development of suitable low-cost hole-transporting materials (HTMs). Here, we put forward a new concept of HTMs for PSCs: a 3D structure with a core of coplanar quinolizino acridine, derived from the conventional concept of 2D triphenylamine HTMs. A cheaper Ag nanolayer was utilized to replace Au as the counter electrodes, and the title HTM TDT-OMeTAD was synthesized via an easy four-step synthesis (total yield: 61%) to achieve the low cost and convenient manufacture of PSCs. Compared with the conventional 2D triphenylamine HTM, TTPA-OMeTPA, PSC devices based on the 3D HTM TDT-OMeTPA showed a significant improvement in PCE from 10.8% to 16.4%, even outperforming Spiro-OMeTAD (14.8%). TDT-OMeTAD's highest PCE mainly results from it having the highest open-circuit voltage (Voc) of 1.01 V in this work, which is proven to be due to the higher hole mobility, matching energy levels, higher hydrophobicity and the smaller dark current. Moreover, an incident photon-current conversion efficiency (IPCE) test and time-resolved photoluminescence (TRPL) have been carried out to observe the better hole injecting efficiency and photoelectric conversion capability of TDT-OMeTPA based PSCs than Spiro-OMeTAD. The TDT-OMeTPA based PSCs exhibited >75% reproducibility (PCE > 15%) and retained 93.2% of the initial PCE after >500 hours.