Targeting interleukin-33 and thymic stromal lymphopoietin pathways for novel pulmonary therapeutics in asthma and COPD.

Interleukin-33 (IL-33) and thymic stromal lymphopoietin (TSLP) are alarmins that are released upon airway epithelial injury from insults such as viruses and cigarette smoke, and play critical roles in the activation of immune cell populations such as mast cells, eosinophils and group 2 innate lymphoid cells. Both cytokines were previously understood to primarily drive type 2 (T2) inflammation, but there is emerging evidence for a role for these alarmins to additionally mediate non-T2 inflammation, with recent clinical trial data in asthma and COPD cohorts with non-T2 inflammation providing support. Currently available treatments for both COPD and asthma provide symptomatic relief with disease control, improving lung function and reducing exacerbation rates; however, there still remains an unmet need for further improving lung function and reducing exacerbations, particularly for those not responsive to currently available treatments. The epithelial cytokines/alarmins are involved in exacerbations; biologics targeting TSLP and IL-33 have been shown to reduce exacerbations in moderate-to-severe asthma, either in a broad population or in specific subgroups, respectively. For COPD, while there is clinical evidence for IL-33 blockade impacting exacerbations in COPD, clinical data from anti-TSLP therapies is awaited. Clinical data to date support an acceptable safety profile for patients with airway diseases for both anti-IL-33 and anti-TSLP antibodies in development. We examine the roles of IL-33 and TSLP, their potential use as drug targets, and the evidence for target patient populations for COPD and asthma, together with ongoing and future trials focused on these targets.

An Integrated Multi-omic Single-Cell Atlas of Human B Cell Identity.

B cells are capable of a wide range of effector functions including antibody secretion, antigen presentation, cytokine production, and generation of immunological memory. A consistent strategy for classifying human B cells by using surface molecules is essential to harness this functional diversity for clinical translation. We developed a highly multiplexed screen to quantify the co-expression of 351 surface molecules on millions of human B cells. We identified differentially expressed molecules and aligned their variance with isotype usage, VDJ sequence, metabolic profile, biosynthesis activity, and signaling response. Based on these analyses, we propose a classification scheme to segregate B cells from four lymphoid tissues into twelve unique subsets, including a CD45RB+CD27- early memory population, a class-switched CD39+ tonsil-resident population, and a CD19hiCD11c+ memory population that potently responds to immune activation. This classification framework and underlying datasets provide a resource for further investigations of human B cell identity and function.

An earthworm-inspired soft robot with perceptive artificial skin.

The bodies of earthworms are composed of repeating deformable structural units, called metameres, that generate the peristaltic body motions required for limbless underground burrowing and above-ground crawling. Metameres are actuated by circular and longitudinal muscles that are activated synchronously by the animals' nervous systems. A significant number of the neural-motor feedback loops function with sensory input gathered by the animals' highly sensitive skins, which are embedded with light, pressure and chemical receptors. In this paper, adopting the basic mechanisms employed by earthworms, we propose a new type of pneumatically-driven soft robot that can travel inside pipes by mimicking the motions and replicating the functionalities of a single metamere. Furthermore, we introduce a sensing scheme for feedback control that mimics the mechanical sensory capabilities of an earthworm's skin, which was developed upon stretchable liquid circuits capable of measuring strain and detecting pressure variations. The suitability of the proposed approach is demonstrated through several controlled locomotion experiments, employing two different robotic prototypes.

An earthworm-inspired friction-controlled soft robot capable of bidirectional locomotion.

We present the design, fabrication, modeling and feedback control of an earthworm-inspired soft robot capable of bidirectional locomotion on both horizontal and inclined flat platforms. In this approach, the locomotion patterns are controlled by actively varying the coefficients of friction between the contacting surfaces of the robot and the supporting platform, thus emulating the limbless locomotion of earthworms at a conceptual level. Earthworms are characterized by segmented body structures, known as metameres, composed of longitudinal and circular muscles which during locomotion are contracted and relaxed periodically in order to generate a peristaltic wave that propagates backwards with respect to the worm's traveling direction; simultaneously, microscopic bristle-like structures (setae) on each metamere coordinately protrude or retract to provide varying traction with the ground, thus enabling the worm to burrow or crawl. The proposed soft robot replicates the muscle functionalities and setae mechanisms of earthworms employing pneumatically-driven actuators and 3D-printed casings. Using the notion of controllable subspace, we show that friction plays an indispensable role in the generation and control of locomotion in robots of this type. Based on this analysis, we introduce a simulation-based method for synthesizing and implementing feedback control schemes that enable the robot to generate forward and backward locomotion. From the set of feasible control strategies studied in simulation, we adopt a friction-modulation-based feedback control algorithm which is implementable in real time and compatible with the hardware limitations of the robotic system. Through experiments, the robot is demonstrated to be capable of bidirectional crawling on surfaces with different textures and inclinations.