Search

One of the challenges in studying islet inflammation–insulitis–is that it is a transient phenomenon. Traditional reporting of the insulitis progression is based on cumulative, donor-averaged values of leucocyte density in the vicinity of pancreatic islets, that hinder intra- and inter-islet heterogeneity of disease progression. Here, we aimed to understand why insulitis is non-uniform, often with peri-insulitis lesions formed on one side of an islet. To achieve this, we demonstrated the applicability of network theory in detangling intra-islet multi-cellular interactions during insulitis. Specifically, we asked the question “What is unique about regions of the islet that interact with immune cells first”. This study utilized the non-obese diabetic mouse model of type one diabetes and examined the interplay among α-, β-, T-cells, myeloid cells, and macrophages in pancreatic islets during the progression of insulitis. Disease evolution was tracked based on the T/β cell ratio in individual islets. In the early stage, we found that immune cells are preferentially interacting with α-cell-rich regions of an islet. At the islet periphery α-linked β-cells were found to be targeted significantly more compared to those without α-cell neighbors. Additionally, network analysis revealed increased T-myeloid, and T-macrophage interactions with all β-cells.

Anthropogenically-driven changes in seasonal climate patterns are already jeopardizing traditional farming practices all around the world. These climatic changes increasingly expose farmers to challenging conditions, reducing the efficacy of existing farm practices and productivity. There is a plethora of information, tools, and practices that could be useful for farmers trying to respond to climate variability and change, including climate projections, horticultural advances, and agricultural management best practices. Whilst these tools and knowledge exist, they are often not contextualized in ways that equitably facilitate decision-making and action. To ensure weather and climate information services are accessible and useful to farmers, it is critical to understand and integrate considerations for the desired types, timing, and uses of the information. The one-size-fits-all information services that are often available don't account for regional or social differences, local physical conditions, or the needs of different populations. In order to improve our understanding of how weather and climate information services can better cater to farmers' needs when modifying and adapting their goals, risk management, and farm practices, we carried out a household survey in communities across three provinces in Papua New Guinea. The survey was developed to draw out key design considerations for seasonal climate forecasts in terms of timing, type of information, and applications. Based on the clustering and associations of these variables, this study identifies different profiles of information services content. It then examines whether specific profiles are associated with demographic groups or geographic locations. The findings demonstrate gender and geographic differences in the desired bundles of weather and climate information, and therefore can help to pinpoint specific components that would be beneficial to incorporate into extension and outreach programmes in different contexts within Papua New Guinea. This study highlights the value of tailoring weather and climate information services with specific groups of farmers, thereby enabling more equitable access to and use of critical knowledge for smallholders to build the capacity, knowledge, and systems to strategically adapt to climate change. At the same time, this study illustrates areas to gain efficiency and potentially scale up the provision of climate information services.

Naïve T cell activation in secondary lymphoid organs such as lymph nodes (LNs) occurs upon recognition of cognate antigen presented by antigen presenting cells (APCs). T cell activation requires cytoskeleton rearrangement and sustained interactions with APCs. Enabled/vasodilator-stimulated phosphoprotein (Ena/VASP) proteins are a family of cytoskeletal effector proteins responsible for actin polymerization and are frequently found at the leading edge of motile cells. Ena/VASP proteins have been implicated in motility and adhesion in various cell types, but their role in primary T cell interstitial motility and activation has not been explored. Our goal was to determine the contribution of Ena/VASP proteins to T cell–APC interactions, T cell activation, and T cell expansion in vivo. Our results showed that naïve T cells from Ena/VASP-deficient mice have a significant reduction in antigen-specific T cell accumulation following Listeria monocytogenes infection. The kinetics of T cell expansion impairment were further confirmed in Ena/VASP-deficient T cells stimulated via dendritic cell immunization. To investigate the cause of this T cell expansion defect, we analyzed T cell–APC interactions in vivo by two-photon microscopy and observed fewer Ena/VASP-deficient naïve T cells interacting with APCs in LNs during priming. We also determined that Ena/VASP-deficient T cells formed conjugates with significantly less actin polymerization at the T cell–APC synapse, and that these conjugates were less stable than their WT counterparts. Finally, we found that Ena/VASP-deficient T cells have less LFA-1 polarized to the T cell–APC synapse. Thus, we conclude that Ena/VASP proteins contribute to T cell actin remodeling during T cell–APC interactions, which promotes the initiation of stable T cell conjugates during APC scanning. Therefore, Ena/VASP proteins are required for efficient activation and expansion of T cells in vivo.

The Indo-Pacific is a region of the world experiencing rapid growth in population and development. However, it is also exposed to a number of social, economic, geopolitical, and biophysical stressors, which may undermine the region's ability to support its population, ensure food security, and sustain livelihoods. In response to the complex suite of stressors, a number of development initiatives and research programs have been established to build resilience in the region's food systems. These initiatives vary in scope and scale, but also in what they mean by the term resilience and the components of the food system they address. This variation has implications for the outcomes of these efforts and how well they match a theoretical ideal of resilience. This review examines how resilience and food systems are defined, conceptualized, and applied within research studies and projects or initiatives on food systems resilience funded or supported by national, regional, or multilateral government, and non-governmental institutions in the Indo-Pacific region. It also compares how the concepts are treated from an academic or theoretical perspective vs. in practical applications. We take a two-pronged approach: first, identifying organizations engaged in the Indo-Pacific region and developing an inventory of initiatives and projects that have bearing on food systems resilience; and second, carrying out literature searches to record research studies in the region that examine resilience within food systems. We then identify any formalized frameworks or definitions of resilience and/or food systems guiding these projects and studies. The results indicate there is a heavy focus on climate change and natural disasters, and to a lesser extent health-related shocks, in food systems resilience research and practice. Definitions, however, are inconsistently reported, and are often more simplistic than resilience theory depicts, favoring resilience conceptualizations around adaptation and a production-oriented food systems framing. While the specific definitions vary between research and applied projects, the fragmented and ambiguous use of terms presents a challenge for policy applications and coordination. Overall, establishing some clear guiding resilience principles, modified according to contextual factors, could enable more streamlined resilience work in Indo-Pacific food systems.

T cells and B cells have been identified in human and murine islets, but the phenotype and role of islet lymphocytes is unknown. Resident immune populations set the stage for responses to inflammation in the islets during homeostasis and diabetes. Thus, we sought to identify the phenotype and effector function of islet lymphocytes to better understand their role in normal islets and in islets under metabolic stress. Lymphocytes were located in the islet parenchyma, and were comprised of a mix of naïve, activated, and memory T cell and B cell subsets, with an enrichment for regulatory B cell subsets. Use of a Nur77 reporter indicated that CD8 T cells and B cells both received local antigen stimulus, indicating that they responded to antigens present in the islets. Analysis of effector function showed that islet T cells and B cells produced the regulatory cytokine IL-10. The regulatory phenotype of islet T cells and B cells and their response to local antigenic stimuli remained stable under conditions of metabolic stress in the diet induced obesity (DIO) model. T cells present in human islets retained a similar activated and memory phenotype in non-diabetic and T2D donors. Under steady-state conditions, islet T cells and B cells have a regulatory phenotype, and thus may play a protective role in maintaining tissue homeostasis.

Type 1 diabetes (T1D) is a T cell mediated autoimmune disease that affects more than 19 million people with incidence increasing rapidly worldwide. For T cells to effectively drive T1D, they must first traffic to the islets and extravasate through the islet vasculature. Understanding the cues that lead to T cell entry into inflamed islets is important because diagnosed T1D patients already have established immune infiltration of their islets. Here we show that CD11c+ cells are a key mediator of T cell trafficking to infiltrated islets in non-obese diabetic (NOD) mice. Using intravital 2-photon islet imaging we show that T cell extravasation into the islets is an extended process, with T cells arresting in the islet vasculature in close proximity to perivascular CD11c+ cells. Antigen is not required for T cell trafficking to infiltrated islets, but T cell chemokine receptor signaling is necessary. Using RNAseq, we show that islet CD11c+ cells express over 20 different chemokines that bind chemokine receptors expressed on islet T cells. One highly expressed chemokine-receptor pair is CXCL16-CXCR6. However, NOD. CXCR6−/− mice progressed normally to T1D and CXCR6 deficient T cells trafficked normally to the islets. Even with CXCR3 and CXCR6 dual deficiency, T cells trafficked to infiltrated islets. These data reinforce that chemokine receptor signaling is highly redundant for T cell trafficking to inflamed islets. Importantly, depletion of CD11c+ cells strongly inhibited T cell trafficking to infiltrated islets of NOD mice. We suggest that targeted depletion of CD11c+ cells associated with the islet vasculature may yield a therapeutic target to inhibit T cell trafficking to inflamed islets to prevent progression of T1D.