Redesigning a Street Corridor in San Clemente, CA: South El Camino Real Urban Design Concept Plan

The South El Camino Real Urban Design Concept Plan was developed by a first-year MCRP studio for the City of San Clemente, CA. The San Clemente community, the City planners and the City Council welcomed the students’ ideas for making the corridor appealing, economically attractive, and safer for pedestrians and bicyclists

Impact of morphological features and chemical composition of tendon biomimetic scaffolds on immune recognition via Toll-like receptors

Tendinopathies are a major worldwide clinical problem. The development of tendon biomimetic scaffolds is considered a promising, therapeutic approach. However, to be clinically effective, scaffolds should avoid immunological recognition. It has been well described that scaffolds composed of aligned fibers lead to a better tenocyte differentiation, vitality, proliferation and motility. However, little has been studied regarding the impact of fiber spatial distribution on the recognition by immune cells. Additionally, it has been suggested that higher hydrophilicity would reduce their immune recognition. Herein, polycaprolactone (PCL)–hyaluronic acid (HA)-based electrospun scaffolds were generated with different fiber diameters (in the nano- and micro-scales) and orientations as well as different grades of wettability and the impact of these properties on immunological recognition has been assessed, by means of Toll-like receptor (TLR) reporter cells. Our results showed that TLR 2/1 and TLR 2/6 were not triggered by the scaffolds. In addition, the TLR 4 signalling pathway seems to be triggered to a greater extent by higher PCL and HA concentrations, but the alignment of the fibers prevents the triggering of this receptor. Taken together, TLR reporter cells were shown to be a useful and effective tool to study the potential of scaffolds to induce immune responses and the results obtained can be used to inform the design of fibrous scaffolds for tendon repair.This work demonstrates that scaffolds’ fiber alignment has an impact on the immune recognition of the scaffolds and presents TLR reporter cells as a simple and fast read out system for analyzing the recognition of the scaffolds by TLRs.Horizon 2020 Framework Programme 10.13039/10001066

Antibody agonists trigger immune receptor signaling through local exclusion of receptor-type protein tyrosine phosphatases

Antibodies can block immune receptor engagement or trigger the receptor machinery to initiate signaling. We hypothesized that antibody agonists trigger signaling by sterically excluding large receptor-type protein tyrosine phosphatases (RPTPs) such as CD45 from sites of receptor engagement. An agonist targeting the costimulatory receptor CD28 produced signals that depended on antibody immobilization and were sensitive to the sizes of the receptor, the RPTPs, and the antibody itself. Although both the agonist and a non-agonistic anti-CD28 antibody locally excluded CD45, the agonistic antibody was more effective. An anti–PD-1 antibody that bound membrane-proximally excluded CD45, triggered SHP2 phosphatase recruitment, and suppressed systemic lupus erythematosus and delayed-type hypersensitivity in experimental models. Paradoxically, nivolumab and pembrolizumab, anti–PD-1 blocking antibodies used clinically, also excluded CD45 and were agonistic in certain settings. Reducing these agonistic effects using antibody engineering improved PD-1 blockade. These findings establish a framework for developing new and improved therapies for autoimmunity and cancer