Restoring immunological tolerance in established experimental arthritis by combinatorial citrullinated peptides and immunomodulatory signals

Promoted tolerance is a coveted therapeutic approach for rheumatoid arthritis (RA), as current im-munosuppressive treatments are not disease-specific, primarily targeting the inflammatory response and exerting debilitating side effects. The cellular and antigenic complexity of RA challenges the design of nanoparticle-based tolerogenic strategies to selectively and comprehensively ameliorate joint destruction and restore immune tolerance in RA. Herein, we aimed at exploring the therapeutic effects and tolerogenic mechanism of a novel "tolerogenic polypeptide vaccine" (TPvax), which carried a multiepitope citrullinated peptide (Cit-ME) and rapamycin (Rapa), in established experimental arthritis. A low dose Rapa helped to drive the generation of anti-inflammatory cytokines and tolerogenic dendritic cells (DCs), thereby providing an immunosuppressive microenvironment for tolerance induction. We demonstrated that TPvax enabled the synergism between Cit-ME and Rapa, which led to the upregulation of regulatory T cells (Treg), pro-motion of IL-10 secretion and reduction of pro-inflammatory cytokines and antibody titers. Importantly, we provided evidence of epitope spreading to citrullinated antigens in collagen-induced arthritis (CIA) and demonstrated that co-delivery of Cit-ME and Rapa promoted immune tolerance even during an ongoing inflammatory event. This work would shed light to the development of tolerogenic therapeutics as novel immunotherapies for RA. (c) 2021 Elsevier Ltd. All rights reserved

Curbing opportunism in logistics outsourcing relationships: The role of relational norms and contract

Logistics outsourcing, as a strategy to obtain competitive advantages, is prevalent in today's business world. However, we know little about logistics outsourcing, especially with regard to opportunistic behavior types and their relational antecedents (e.g., contracts and relational norms) of their opportunism in the third party logistics (3PL) user-provider relationships in emerging economies. Using China's developing 3PL industry as a research context, and social exchange theory and transaction cost economics as the theoretical lenses, we examine how three dimensions of relational norms (information exchange, flexibility, solidarity) influence two dimensions of contracts (detailed contracts, contract application), and how relational norms and contracts simultaneously influence 3PL providers’ opportunism. Using data collected from 247 manufacturing and service firms in China, we empirically test the proposed model and find that detailed contracts and solidarity are effective safeguards in reducing 3PL providers’ opportunistic behavior, while the contract application process leads to opportunism. Furthermore, flexibility is positively related to detailed contracts and the contract application process, which can influence 3PL providers’ opportunism negatively and positively, respectively. This study contributes to the logistics outsourcing, opportunism, and relationship management literature and provides managerial implications for 3PL practices in China