Explore the vast range of titles available.

Cell-based cancer immunotherapy has achieved significant advancements, providing a source of hope for cancer patients. Notwithstanding the considerable progress in cell-based immunotherapy, the persistently low response rates and the exorbitant costs associated with their implementation still present a formidable challenge in clinical settings. In the landscape of cell-based cancer immunotherapies, an uncharted territory involves Type 2 innate lymphoid cells (ILC2s) and interleukin-33 (IL-33) which promotes ILC2 functionality, recognized for their inherent ability to enhance immune responses. Recent discoveries regarding their role in actuating cytolytic T lymphocyte responses, including curbing tumor growth rates and hindering metastasis, have added a new dimension to our understanding of the IL-33/ILC2 axis. These recent insights may hold significant promise for ILC2 cell-based immunotherapy. Nevertheless, the prospect of adoptively transferring ILC2s to confer immune protection against tumors has yet to be investigated. The present study addresses this hypothesis, revealing that ILC2s isolated from the lungs of tumor-bearing mice, and tumor infiltrating ILC2s when adoptively transferred after tumor establishment at a ratio of one ILC2 per sixty tumor cells, leads to an influx of tumor infiltrating CD4+ and CD8+ T lymphocytes as well as tumor infiltrating eosinophils resulting in a remarkable reduction in tumor growth. Moreover, we find that post-adoptive transfer of ILC2s, the number of tumor infiltrating ILC2s is inversely proportional to tumor size. Finally, we find corollaries of the IL-33/ILC2 axis enhancing the infiltration of eosinophils in human prostate carcinomas patients' expressing high levels of IL-33 versus those expressing low levels of IL-33. Our results underscore the heightened efficacy of adoptively transferred ILC2s compared to alternative approaches, revealing an approximately one hundred fifty-fold superiority on a cell-per-cell basis over CAR T-cells in the specific targeting and elimination of tumors within the same experimental model. Overall, this study demonstrates the functional significance of ILC2s in cancer immunosurveillance and provides the proof of concept of the potential utility of ILC2 cell-based cancer immunotherapies.

Chronic rhinosinusitis (CRS) is a prevalent and complex inflammatory disease within otolaryngology, traditionally classified into phenotypes based on the presence (CRSwNP) or absence (CRSsNP) of nasal polyps. However, these phenotypic classifications inadequately capture the underlying pathophysiological heterogeneity of CRS. Recently, immune-inflammatory endotyping has emerged as a pivotal approach to better characterize CRS by delineating distinct inflammatory pathways, primarily type 1, type 2, and type 3 immune responses, each driven by unique immune cells and cytokine profiles. Epithelial-derived cytokines such as thymic stromal lymphopoietin (TSLP), IL-33, and IL-25, alongside immune cells including group 2 innate lymphoid cells (ILC2), T helper 2 (Th2), and Th17 cells, play critical roles in modulating the immune landscape of CRS. Moreover, variations in immune responses among different populations highlight the disease’s heterogeneity and underscore the need for precise immunological characterization. This review comprehensively summarizes recent advances in the immune-inflammatory endotyping of CRS, elucidates the underlying immunopathogenic mechanisms, and discusses the clinical significance of these endotypes. By integrating current research findings, this article aims to provide a theoretical foundation for the development of personalized therapeutic strategies tailored to distinct immune-inflammatory profiles in CRS patients.

The concept of innate lymphoid cells (ILCs) includes both conventional natural killer (NK) cells and helper ILCs, which resemble CD8+ killer T cells and CD4+ helper T cells in acquired immunity, respectively. Conventional NK cells are migratory cytotoxic cells that find tumor cells or cells infected with microbes. Helper ILCs are localized at peripheral tissue and are responsible for innate helper-cytokine production. Helper ILCs are classified into three subpopulations: TH1-like ILC1s, TH2-like ILC2s, and TH17/TH22-like ILC3s. Because of the functional similarities between ILCs and T cells, ILCs can serve as an innate component that augments each corresponding type of acquired immunity. However, the physiological functions of ILCs are more plastic and complicated than expected and are affected by environmental cues and types of inflammation. Here, we review recent advances in understanding the interaction between ILCs and acquired immunity, including T- and B-cell responses at various conditions. Immune suppressive activities by ILCs in particular are discussed in comparison to their immune stimulatory effects to gain precise knowledge of ILC biology and the physiological relevance of ILCs in human diseases.

Rhinoviruses are the major cause of asthma exacerbations; however, its underlying mechanisms are poorly understood. We hypothesized that the epithelial cell-derived cytokine IL-33 plays a central role in exacerbation pathogenesis through augmentation of type 2 inflammation. To assess whether rhinovirus induces a type 2 inflammatory response in asthma in vivo and to define a role for IL-33 in this pathway. We used a human experimental model of rhinovirus infection and novel airway sampling techniques to measure IL-4, IL-5, IL-13, and IL-33 levels in the asthmatic and healthy airways during a rhinovirus infection. Additionally, we cultured human T cells and type 2 innate lymphoid cells (ILC2s) with the supernatants of rhinovirus-infected bronchial epithelial cells (BECs) to assess type 2 cytokine production in the presence or absence of IL-33 receptor blockade. IL-4, IL-5, IL-13, and IL-33 are all induced by rhinovirus in the asthmatic airway in vivo and relate to exacerbation severity. Further, induction of IL-33 correlates with viral load and IL-5 and IL-13 levels. Rhinovirus infection of human primary BECs induced IL-33, and culture of human T cells and ILC2s with supernatants of rhinovirus-infected BECs strongly induced type 2 cytokines. This induction was entirely dependent on IL-33. IL-33 and type 2 cytokines are induced during a rhinovirus-induced asthma exacerbation in vivo. Virus-induced IL-33 and IL-33-responsive T cells and ILC2s are key mechanistic links between viral infection and exacerbation of asthma. IL-33 inhibition is a novel therapeutic approach for asthma exacerbations.

[This corrects the article DOI: 10.3389/fimmu.2025.1568062.].

Interleukin (IL)-18 was originally discovered as a factor that enhances interferon (IFN)-γ production by anti-CD3-stimulated Th1 cells, particularly in association with IL-12. IL-12 is a cytokine that induces development of Th1 cells. IL-18 cannot induce Th1 cell development, but has the capacity to activate established Th1 cells to produce IFN-γ in the presence of IL-12. Thus, IL-18 is regarded as a proinflammatory cytokine that facilitates type 1 responses. However, in the absence of IL-12 but presence of IL-2, IL-18 stimulates natural killer cells, NKT cells, and even established Th1 cells to produce IL-3, IL-9, and IL-13. Thus, IL-18 also facilitates type 2 responses. This unique function of IL-18 contributes to infection-associated allergic diseases. Together with IL-3, IL-18 stimulates mast cells and basophils to produce IL-4, IL-13, and chemical mediators such as histamine. Thus, IL-18 also induces innate-type allergic inflammation. IL-18 belongs to the IL-1 family of cytokines, which share similar molecular structures, receptors structures, and signal transduction pathways. Nevertheless, IL-18 shows a unique function by binding to a specific receptor expressed on distinct types of cells. In this review article, I will focus on the unique features of IL-18 in lymphocytes, basophils, and mast cells, particularly in comparison with IL-33.

Background Group 2 innate lymphoid cells (ILC2s) are critical sources of type 2 cytokines and represent one of the major tissue-resident lymphoid cells in the mouse lung. However, the molecular mechanisms underlying ILC2 activation under challenges are not fully understood. Results Here, using single-cell transcriptomics, genetic reporters, and gene knockouts, we identify four ILC2 subsets, including two non-activation subsets and two activation subsets, in the mouse acute inflammatory lung. Of note, a distinct activation subset, marked by the transcription factor Nr4a1, paradoxically expresses both tissue-resident memory T cell (Trm), and effector/central memory T cell (Tem/Tcm) signature genes, as well as higher scores of proliferation, activation, and wound healing, all driven by its particular regulons. Furthermore, we demonstrate that the Nr4a1 + ILC2s are restrained from activating by the programmed cell death protein-1 (PD-1), which negatively modulates their activation-related regulons. PD-1 deficiency places the non-activation ILC2s in a state that is prone to activation, resulting in Nr4a1 + ILC2 differentiation through different activation trajectories. Loss of PD-1 also leads to the expansion of Nr4a1 + ILC2s by the increase of their proliferation ability. Conclusions The findings show that activated ILC2s are a heterogenous population encompassing distinct subsets that have different propensities, and therefore provide an opportunity to explore PD-1's role in modulating the activity of ILC2s for disease prevention and therapy.

is a zoonotic pathogen capable of invading the host through the intestinal mucosa. However, the immune mechanisms underlying intestinal infection remain poorly understood. Tuft cells are specialized chemosensory epithelial cells in the intestine that can detect pathogen invasion and secrete IL-25, subsequently activating type 2 innate lymphoid cells (ILC2s) and playing a critical role in anti-parasitic immune responses. Nevertheless, whether the tuft cell-ILC2 circuit participates in immune responses against bacterial infections remains unclear. This study aimed to investigate the dynamic changes of tuft cells and ILC2s following infection, with a particular focus on elucidating the regulatory role of IL-25 in this process. Thirty-six mice were divided into six groups: normal control (NC), isotype control (IC), infection groups at different time points (3, 7, and 14 days post-infection, designated as Inf-3d, Inf-7d, and Inf-14d, respectively), and an IL-25 blockade group (IL-25 Blk-7d, in which mice received anti-IL-25 neutralizing antibody treatment prior to infection and were analyzed at 7 days post-infection). In this study, immunofluorescence assay, flow cytometry, and Western blot were employed to detect the dynamic changes of tuft cells and ILC2s in intestinal tissues, as well as to determine the expression levels of pathway-related proteins. The results showed that the numbers of tuft cells and ILC2s in the mouse intestine increased following infection, peaking at 7 days post-infection. Pretreatment with IL-25 neutralizing antibody significantly suppressed the proliferation of these two cell populations. Western blot analysis further confirmed that the expression levels of tuft cell-associated proteins (PO2F3, DCLK1, and IL-25) and ILC2-associated proteins (GATA3 and IL-13) were upregulated in infected intestinal tissues, whereas IL-25 blockade treatment inhibited the expression of these proteins. Correlation analysis revealed a remarkably strong positive correlation between the proportions of tuft cells and ILC2s, and this correlation was completely abolished following IL-25 neutralization. These findings confirm that the activation of the tuft cell-ILC2 circuit is dependent on the regulatory role of IL-25. These findings extend the antimicrobial role of the tuft cell-ILC2 circuit beyond parasitic immunity and identify IL-25 as an essential regulatory mediator in antibacterial defense at the intestinal mucosa.

Purpose of ReviewThe incidence of allergic diseases such as asthma, rhinitis and atopic dermatitis has risen at an alarming rate over the last century. Thus, there is a clear need to understand the critical factors that drive such pathologic immune responses. Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a nuclear receptor that has emerged as an important regulator of multiple cell types involved in the inflammatory response to allergens; from airway epithelial cells to T Helper (TH) cells.Recent FindingsInitial studies suggested that agonists of PPAR-γ could be employed to temper allergic inflammation, suppressing pro-inflammatory gene expression programs in epithelial cells. Several lines of work now suggest that PPAR-γ plays an essential in promoting ‘type 2’ immune responses that are typically associated with allergic disease. PPAR-γ has been found to promote the functions of TH2 cells, type 2 innate lymphoid cells, M2 macrophages and dendritic cells, regulating lipid metabolism and directly inducing effector gene expression. Moreover, preclinical models of allergy in gene-targeted mice have increasingly implicated PPAR-γ in driving allergic inflammation.SummaryHerein, we highlight the contrasting roles of PPAR-γ in allergic inflammation and hypothesize that the availability of environmental ligands for PPAR-γ may be at the heart of the rise in allergic diseases worldwide.

Allergic diseases are significant diseases that affect many patients worldwide. In the past few decades, the incidence of allergic diseases has increased significantly due to environmental changes and social development, which has posed a substantial public health burden and even led to premature death. The understanding of the mechanism underlying allergic diseases has been substantially advanced, and the occurrence of allergic diseases and changes in the immune system state are known to be correlated. With the identification and in-depth understanding of innate lymphoid cells, researchers have gradually revealed that type 2 innate lymphoid cells (ILC2s) play important roles in many allergic diseases. However, our current studies of ILC2s are limited, and their status in allergic diseases remains unclear. This article provides an overview of the common phenotypes and activation pathways of ILC2s in different allergic diseases as well as potential research directions to improve the understanding of their roles in different allergic diseases and ultimately find new treatments for these diseases.