Yeganeh Mehrani

Two key players in the immune system, dendritic cells (DCs) and innate lymphoid cells (ILCs), interact in a crucial way to fight infectious diseases. DCs play a key role in recognizing pathogens, and ILCs respond to cytokines released by DCs. This response triggers the production of specific effector cytokines that help control pathogens and maintain the body’s barrier integrity. DCs have various receptors, including Toll-like receptors (TLRs), that detect microbial components and trigger immune responses. Likewise, ILCs act as essential initial responders in the immune system in viral, bacterial, and parasitic infections. Successfully managing diseases caused by pathogens mainly depends on the combined actions of DCs and ILCs, which work to suppress and eliminate pathogens. DCs also play a crucial role in activating innate and adaptive immune cell subsets, including ILCs. Furthermore, the use of DCs in developing vaccines and immunotherapy for cancers, along with the dedication of many researchers to improve immune responses through DCs, has increased interest in the potential of DC therapies for treating and preventing infectious diseases. This review examines approaches that may enhance DC vaccines and boost anti-infection immune responses by fostering better interactions of DCs with ILCs.

Dendritic cell (DC) vaccines stimulate the immune system to target cancer antigens, representing a promising option for immunotherapy. However, clinical trials have demonstrated limited effectiveness, emphasizing the need for enhanced immune responses. Improving the production of DC vaccines, assessing their impact on immune components, and observing responses could improve the results of DC-based therapies. Innate lymphoid cells (ILCs) represent a heterogeneous population of innate immune components that generate cytokines and modulate the immune system, potentially enhancing immunotherapies. Recent research highlights the different functions of ILCs in cancer, demonstrating their dual capabilities to promote tumors and exhibit anti-tumor actions. DCs and ILCs actively communicate under physiological and pathological conditions, and the activation of ILCs by DCs or DC vaccines has been shown to influence ILC cytokine production and function. Gaining insights into the interaction between DC-activated ILCs and tumors is essential for creating exciting new therapeutic strategies. These strategies aim to boost anti-tumor immunity while reducing the support that tumors receive. This review examines the effect of DC vaccination on host ILCs, illustrating the complex relationship between DC-based vaccines and ILCs. Furthermore, it explores some exciting strategies to enhance DC vaccines, aiming to boost anti-tumor immune responses by fostering better engagement with ILCs.

Canine mast cell tumours (MCTs) are one of the most common skin cancers of dogs. Surgical removal is the primary treatment, but recurrence and metastasis can occur even with low‐grade tumours. As a result, new treatment strategies are being sought. We tested the potential of several oncolytic viruses (OVs) to infect and kill a cell line isolated from a canine MCT. Employing a resazurin‐based metabolic assay and flow cytometry technology, we used recombinant vesicular stomatitis virus (rVSV‐Δm51), avian orthoavulavirus‐1 (AOaV‐1), and Orf viruses in our assessment. Our study aimed to evaluate the potential of oncolytic virotherapy in treating canine cancers. We found that MCT‐1 cells showed different sensitivities to the OVs, with rVSV‐Δm51 showing the most promising results in vitro. These findings suggest that further investigation into using OVs for treating canine MCTs is needed, although clinical efficacy is yet to be determined.

Rhabdoviral vectors can induce lysis of cancer cells. While studied almost exclusively at 37 °C, viruses are subject to a range of temperatures in vivo, including temperatures ≤31 °C. Despite potential implications, the effect of temperatures in vivo where therapeutic windows are limited.

The skin is a dynamic organ with a complex immune network critical for maintaining balance and defending against various pathogens. Different types of cells in the skin, such as mast cells (MCs) and group 2 innate lymphoid cells (ILC2s), contribute to immune regulation and play essential roles in the early immune response to various triggers, including allergens. It is beneficial to dissect cell-to-cell interactions in the skin to elucidate the mechanisms underlying skin immunity. The current manuscript concentrates explicitly on the communication pathways between MCs and ILC2s in the skin, highlighting their ability to regulate immune responses, inflammation, and tissue repair. Furthermore, it discusses how the interactions between MCs and ILC2s play a crucial role in various skin conditions, such as autoimmune diseases, dermatological disorders, and allergic reactions. Understanding the complex interactions between MCs and ILC2s in different skin conditions is crucial to developing targeted treatments for related disorders. The discovery of shared pathways could pave the way for novel therapeutic interventions to restore immunological balance in diseased skin tissues.

Dendritic cell (DC) vaccines can stimulate the immune system to target cancer antigens, making them a promising therapy in immunotherapy. Clinical trials have shown limited effectiveness of DC vaccines, highlighting the need to enhance the immune responses they generate. Innate lymphoid cells (ILCs) are a diverse group of innate leukocytes that produce various cytokines and regulate the immune system. These cells have the potential to improve immunotherapies. There is not much research on how group 2 ILCs (ILC2s) communicate with DC vaccines. Therefore, examining the roles of DC vaccination in immune responses is crucial. Our research analyzed the effects of DC vaccination on the ILC2 populations and their cytokine production. By exploring the relationship between ILC2s and DCs, we aimed to understand how this could affect DC-based immunotherapies. The results showed an increase in the number of ILC2s in the local draining lymph node and spleen of tumor-free mice, as well as in the lungs of mice challenged with tumors in a pulmonary metastasis model. This suggests a complex interplay between DC-based vaccines and ILC2s, which is further influenced by the presence of tumors.

Mat cells (MCs) are located in the skin and mucous membranes at points where the body meets the environment. When activated, MCs release inflammatory cytokines, which help the immune system to fight viruses. MCs produce, and have receptors for interferons (IFNs), which belong to a family of cytokines recognized for their antiviral properties. Previously, we reported that MCs produced proinflammatory cytokines in response to a recombinant vesicular stomatitis virus (rVSVΔm51) and that IFNAR signaling was required to down-modulate these responses. Here, we have demonstrated that UV-irradiated rVSVΔm51 did not cause any inflammatory cytokines in either in vitro cultured mouse IFNAR-intact (IFNAR+/+), or in IFNAR-knockout (IFNAR−/−) MCs. However, the non-irradiated virus was able to replicate more effectively in IFNAR−/− MCs and produced a higher level of inflammatory cytokines compared with the IFNAR+/+ MCs. Interestingly, MCs lacking IFNAR expression displayed reduced levels of reactive oxygen species (ROS) compared with IFNAR+/+ MCs. Additionally, upon the viral infection, these IFNAR−/− MCs were found to coexist with many dying cells within the cell population. Based on our findings, IFNAR-intact MCs exhibit a lower rate of rVSVΔm51 infectivity and lower levels of cytokines while demonstrating higher levels of ROS. This suggests that MCs with intact IFNAR signaling may survive viral infections by producing cell-protective ROS mechanisms and are less likely to die than IFNAR−/− cells.

Mast cells (MCs) are abundant at sites exposed to the external environment and pathogens. Local activation of these cells, either directly via pathogen recognition or indirectly via interaction with other activated immune cells and results in the release of pre-stored mediators in MC granules. The release of these pre-stored mediators helps to enhance pathogen clearance. While MCs are well known for their protective role against parasites, there is also significant evidence in the literature demonstrating their ability to respond to viral, bacterial, and fungal infections. Vitamin D is a fat-soluble vitamin and hormone that plays a vital role in regulating calcium and phosphorus metabolism to maintain skeletal homeostasis. Emerging evidence suggests that vitamin D also has immunomodulatory properties on both the innate and adaptive immune systems, making it a critical regulator of immune homeostasis. Vitamin D binds to its receptor, called the vitamin D receptor (VDR), which is present in almost all immune system cells. The literature suggests that a vitamin D deficiency can activate MCs, and vitamin D is necessary for MC stabilization. This manuscript explores the potential of vitamin D to regulate MC activity and combat pathogens, with a focus on its ability to fight viruses.

Osteoarthritis (OA) is the most common degenerative joint disease that causes chronic pain and disability. Different innate immune components, including macrophages, T cells, and neutrophils, participate in OA pathophysiology. Neutrophils are the most abundant circulating leukocytes with multiple specialized functions contributing to innate and adaptive immune functions. Although neutrophils produce proinflammatory cytokines and chemokines, reactive oxygen species (ROS), matrix-degrading enzymes, and neutrophil extracellular traps (NET) that promote joint degradation as the first recruit cells in an inflamed joint, these cells also play an important role in joint repair by regulating the immune response, releasing anti-inflammatory factors, and activating certain protective genes. In this review, various aspects of neutrophil biology, their role in inflammation and its association with OA, and possible therapeutic approaches to target neutrophils for the treatment of OA are described. Since neutrophils play a complex role in the pathophysiology of osteoarthritis, contributing to joint degradation as well as joint repair, targeting these cells is likely to pave the way for a potential therapeutic approach for the management of OA. Future studies are needed to investigate the use of targeted therapies to modulate neutrophil function and identify their subpopulations that are associated with osteoarthritis progression or response to treatment.

Osteoarthritis (OA) is the most common degenerative joint disease that causes chronic pain and disability. Different innate immune components, including macrophages, T cells, and neutrophils, participate in osteoarthritis pathophysiology. Neutrophils are the most abundant circulating leukocytes with multiple specialized functions contributing to innate and adaptive immune functions. Although neutrophils produce proinflammatory cytokines and chemokines, reactive oxygen species (ROS), matrix-degrading enzymes, and neutrophil extracellular traps (NET) that promote joint degradation as the first recruit cells in an inflamed joint, these cells also play an important role in joint repair by regulating the immune response, releasing anti-inflammatory factors, and activating some protective genes. In this review, various aspects of neutrophil biology, their role in inflammation and its association with osteoarthritis, and possible therapeutic approaches to target neutrophils for the treatment of osteoarthritis are described. Understanding neutrophil heterogeneity and their mechanisms of action in joint inflammation, provides a potential strategy for OA management.