Cells In Pathogenesis Research Articles

Exploring the mediating role of immune cells in the pathogenesis of IgA nephropathy through the inflammatory axis of gut microbiota from a genomic perspective.

IgA nephropathy (IgAN) is a chronic glomerular disease characterized by the deposition of IgA antibodies in the kidney's mesangium. Its pathogenesis involves genetic, immune, and environmental factors, particularly within the mucosal immune system and gut microbiota. Immune cells play a central role in mediating these processes, which this study investigates using Mendelian Randomization (MR) to explore causal relationships among gut microbiota, inflammatory markers, blood cells, and immune cells in IgAN pathogenesis. We conducted a two-sample MR analysis using Genome-Wide Association Study (GWAS) summary data to assess the causal effects of gut microbiota, inflammatory markers, and blood cell traits on IgAN. Data sources included the FinnGen dataset for IgAN and relevant GWAS datasets for immune traits, blood cells, and inflammatory markers. Inverse variance weighting (IVW) was the primary MR method, supported by sensitivity analyses. We particularly examined the mediation effect of immune cells on these exposures' influence on IgAN. Significant associations were found between several factors and IgAN. Gut microbiota traits, such as Firmicutes E and Sporomusales, increased IgAN risk, while Citrobacter A and Herbinix reduced it. Inflammatory markers, including Interleukin-10 and Fibroblast Growth Factor 23, promoted IgAN onset. Blood cell traits like red blood cell perturbation response increased risk, while monocyte perturbation response was protective. Immune traits played a key mediating role, with Transitional %B cells reducing IgAN risk and CD28- CD25 + + CD8br %T cells increasing it. This study highlights the pivotal mediating role of immune cells in the interactions between gut microbiota, inflammatory markers, and IgAN risk. These findings identify potential biomarkers and therapeutic targets, providing new insights into the immune mechanisms underlying IgAN and opportunities for intervention.

Using Bioinformatics and Machine Learning to Predict the Genetic Characteristics of Ferroptosis-Cuproptosis-Related Genes Associated with Sleep Deprivation.

Sleep deprivation (SD), a common sleep disease in clinic, has certain risks, and its pathogenesis is still unclear. This study aimed to identify ferroptosis-cuproptosis-related genes (FCRGs) associated with SD through bioinformatics and machine learning, thus elucidating their biological significance and clinical value. SD-DEGs were obtained from GEO. We intersected key WGCNA module genes of DE-FCRGs with SD-DEGs to obtain SD-DE-FCRGs. GO and KEGG analyses were performed. Machine learning was used to screen SD-DE-FCRGs, and filtered genes were intersected to obtain SD characteristic genes. ROC curves were used to evaluate the accuracy of SD characteristic genes. CIBERSORT was used to analyze the correlation between SD-DE-FCRGs and immune cells. We constructed a ceRNA network of SD-DE-FCRGs and used DGIbd to predict gene drug targets. The 156 DEGs were identified from GSE98566. Five SD-DE-FCRGs from DE- FCRGs and SD-DEGs were analyzed via WGCNA, and enrichment analysis involved mainly ribosome regulation, mitochondrial pathways, and neurodegenerative diseases. Machine learning was used to obtain Four SD-DE-FCRGs (IKZF1, JCHAIN, MGST3, and UQCR11), and these gene analyses accurately evaluated the distribution model (AUC=0.793). Immune infiltration revealed that SD hub genes were correlated with most immune cells. Unsupervised cluster analysis revealed significant differential expression of immune-related genes between two subtypes. GSVA and GSEA revealed that enriched biological functions included oxidative phosphorylation, ribonucleic acid, metabolic diseases, activation of oxidative phosphorylation, and other pathways. Four SD-DE-FCRGs associated with 29 miRNAs were identified via the construction of a ceRNA network. The important target lenalidomide of IKZF1 was predicted. We first used bioinformatics and machine learning to screen four SD-DE-FCRGs. These genes may affect the involvement of infiltrating immune cells in pathogenesis of SD by regulating FCRGs. We predicted that lenalidomide may target IKZF1 from SD-DE-FCRGs.

Adenosine A2A receptor activation regulates the M1 macrophages activation to initiate innate and adaptive immunity in psoriasis

Psoriasis is a common inflammatory systemic disease characterized by pro-inflammatory macrophages activation (M1 macrophage) infiltrated in the dermal layer. How M1 macrophage contributes to psoriasis remains unknown. In this study, we found that adenosine A2A receptor (A2AR) agonist CGS 21680 HCl alleviated the imiquimod (IMQ) and mouse IL-23 Protein (rmIL-23)-induced psoriasis inflammation through reducing infiltration of M1. Conversely, Adora2a deletion in mice exacerbated psoriasis-like phenotype. Mechanistically, A2AR activation inhibited M1 macrophage activation via the NF-κB-KRT16 pathway to reduce the secretion of CXCL10/11 and inhibit Th1/17 differentiation. Notably, the KRT16 expression was first found in M1 macrophage in our study, not only in keratinocytes (KCs). CXCL10/11 are first identified as primarily derived from macrophages and dendritic cells (DCs) rather than KCs in psoriasis using single cell RNA sequencing (scRNA-Seq). In total, the study emphasizes the importance of M1 as an innate immune cell in pathogenesis of psoriasis.

Unraveling the role of γδ T cells in the pathogenesis of an oncogenic avian herpesvirus.

Marek's disease virus (MDV) is an oncogenic alphaherpesvirus that causes deadly lymphomas in chickens. In chickens, up to 50% of all peripheral T cells are gamma delta (γδ) T cells. Until now, their role in MDV pathogenesis and tumor formation remains poorly understood. To investigate the role of γδ T cells in MDV pathogenesis, we infected recently generated γδ T cell knockout chickens with very virulent MDV. Strikingly, disease and tumor incidence were highly increased in the absence of γδ T cells, indicating that γδ T cells play an important role in the immune response against MDV. In the absence of γδ T cells, virus replication was drastically increased in the thymus and spleen, which are potential sites of T cell transformation. Taken together, our data provide the first evidence that γδ T cells play an important role in the pathogenesis and tumor formation of this highly oncogenic herpesvirus.IMPORTANCEGamma delta (γδ) T cells are the most abundant T cells in chickens, but their role in fighting pathogens remains poorly understood. Marek's disease virus (MDV) is an important veterinary pathogen, that causes one of the most frequent cancers in animals and is used as a model for virus-induced tumor formation. Our study revealed that γδ T cells play a crucial role in combating MDV, as disease and tumor incidence drastically increased in the absence of these cells. γδ T cells restricted virus replication in the key lymphoid organs, thereby decreasing the likelihood of causing tumors and disease. This study provides novel insights into the role of γδ T cells in the pathogenesis of this highly oncogenic virus.

Psoriatic arthritis subtypes are phenocopied in humanized mice.

Psoriatic arthritis (PsA) is a complex inflammatory disease that challenges diagnosis and complicates the rational selection of effective therapies. Although T cells are considered active effectors in psoriasis and PsA, the role of CD8+ T cells in pathogenesis is not well understood. We selected the humanized mouse model NSG-SGM3 transgenic strain to examine psoriasis and PsA endotypes. Injection of PBMCs and sera from patients with psoriasis and PsA generated parallel skin and joint phenotypes in the recipient mouse. The transfer of human circulating memory T cells was followed by migration and accumulation in the skin and synovia of these immunodeficient mice. Unexpectedly, immunoglobulins were required for recapitulation of the clinical phenotype of psoriasiform lesions and PsA domains (dactylitis, enthesitis, bone erosion). Human CD8+ T cells expressing T-bet, IL-32 and CXCL14 were detected by spatial transcriptomics in murine synovia and by immunofluorescence in the human PsA synovia. Importantly, depletion of human CD8+ T cells prevented skin and synovial inflammation in mice humanized with PsA peripheral blood cells. The humanized model of psoriasis and PsA represents a valid platform for accelerating the understanding of disease pathogenesis, improving the design of personalized therapies, and revealing psoriatic disease targets.

The role of T regulatory cells in pathogenesis of preeclampsia

The role of T regulatory cells in pathogenesis of preeclampsia

The role of B cells in systemic sclerosis.

Systemic sclerosis (SSc) is a rare and refractory systemic disease characterized by fibrosis and vasculopathy in the presence of autoimmune abnormalities. While the exact cause of SSc is incompletely understood, the specific autoantibodies identified in SSc are closely linked to disease severity and prognosis, indicating a significant role of autoimmune abnormalities in the pathogenesis of SSc. Although the direct pathogenic mechanisms of autoantibodies in SSc are not fully elucidated, numerous prior investigations have demonstrated the involvement of B cells in the pathogenesis of SSc through various mechanisms. Additionally, several clinical trials have explored the efficacy of B-cell depletion therapy for SSc, with many reporting positive outcomes. However, the role of B cells in SSc pathogenesis is multifaceted, as they can both promote inflammation and exert inhibitory functions. This article provides an overview of the involvement of B cells in SSc development, incorporating the latest research findings.

Unveiling the role of NK cells, NKT-like cells, and γδ cells in pathogenesis of type 1 reactions in leprosy

Leprosy is a disease with spectral clinical manifestations along with two types of reactions, type 1 reaction (T1R) and type 2 reaction (T2R). T1R especially occurs because of the defensive upgradation of cell-mediated immunity (CMI) to M. leprae antigens. T1R is the main cause of disability in leprosy. The role of conventional adaptive T cells has been well studied to understand T1R. A comprehensive understanding of the role of unconventional T cells in the manifestation of inflammation during T1R is crucial and has not been studied. In our study, we found significantly higher plasma levels of TNFα, IL1β, IL17, and IP10 in T1R when compared to non-reaction (NR). Gene expression for cytokines in blood circulation by qPCR showed significantly higher expression of IFNγ, IP10, TNFα, IL6, IL17A and chemokines CCL3, CCR1, CCR5, and CXCR3 in T1R as compared to NR. Frequencies of NKT-like cells (48.7 %) and NK cells (22.3 %) were found significantly higher in T1R in comparison to NR (36.9 %, 18.3 %, respectively) (p = 0.0001). Significantly lower levels of γδT cells (3.32 %) were observed in T1R in comparison to NR (5.16 %). The present study has provided evidence for the first time on the role of plausible unconventional T cells in the immunopathogenesis of T1R in leprosy.

Comparative Evaluation of Mast Cells in Lichen Planus and Oral Lichenoid Reaction with Giemsa Staining

Introduction: Lichen planus is a relatively common and chronic mucocutaneous disease with unknown. Oral lichenoid reaction is clinical and histopathological similar to lichen planus, but the cause of it is different. Mast cells are responsible for the accumulation of inflammatory cells in the connective tissue. The aim of study was evaluation of the role of mast cells in pathogenesis of two groups of lesions.
 Methods: This cross-sectional study was performed on 26 samples of oral lichen planus, oral lichenoid reaction lesions and 5 samples of irritation fibroma. After the staining with the Giemsa, sections were observed under the optical microscope (x400), and the number of mast cells was counted. The results were analyzed using the SPSS16 software, T test, Mann- Whitney and Chi-squared statistical tests.
 Results: The total number of mast cells and degranulated mast cells in two groups were significantly higher than the control group (P<0/05). Nevertheless, the total number of mast cells, the number of degranulated mast cells and the ratio of degranulated mast cells to the total mast cells had no significant difference between the two groups of lesions. (P> 0/05).
 Conclusion: Mast cells play a role in the pathogenesis of lichen planus and lichenoid reaction lesions. The number of degranulated mast cells and the ratio of degranulated to the total mast cells cannot help to differentiate these two groups of lesions. Clinical examinations and proper history and attention to their etiologic factors have a significant role in differentiating them.

Increased gene expression of CCR6 and RORγt in peripheral blood cells of rheumatoid arthritis patients and their correlation with anti-cyclic citrullinated peptide and disease activity.

The significance of T helper 17 (Th17) cells in the pathogenesis of rheumatoid arthritis (RA) has recently been demonstrated in many studies. Retinoic acid receptor-related orphan receptor γt (RORγt) is a transcription factor that is specifically involved in the generation of Th17 cells. Besides, the chemokine receptor CCR6, the receptor for CCL20, is characteristically expressed by these cells. Considering the pivotal roles of Th17 cells in RA pathogenesis, in this study, we assessed the gene expression of CCR6 and RORγt in the peripheral blood leukocytes of new case RA patients. Also, we evaluated their association with anticyclic citrullinated peptide (anti-CCP) antibodies and disease activity. Forty-five new case RA patients and 45 healthy persons have been recruited in this investigation. The gene expression of CCR6 and RORγt was evaluated by quantitative real-time PCR (qRT-PCR), and anti-CCP antibodies plasma levels were measured using the enzyme-linked immunosorbent assay (ELISA) technique. Disease activity was measured according to the disease activity score-28 (DAS-28) formula. The gene expression of CCR6 and RORγt increased remarkably in new case RA patients compared to healthy controls (p < .05 and p < .01, respectively). Moreover, there was a positive correlation between RORγt gene expression and parameters, including gene expression of CCR6 (p = .001, r = .461), plasma levels of CCL20 (p = .0009, r = .477), ESR (p = .004, r = .419), DAS-28 (p = .006, r = .402), anti-CCP (p = .019, r = .346), and RF (p = .001, r = .451). Also, CCR6 gene expression was positively associated with the DAS-28 (p = .037, r = .310), plasma levels of anti-CCP (p = .037, r = .312), and ESR (p = .029, r = .327). Increased gene expression of CCR6 and RORγt in peripheral blood leukocytes of new case RA patients may contribute to the exacerbation and pathogenesis of RA.

Exploring the Dynamic Role of Gamma-Delta T Cells in Clinical Pathology: A Systematic Review of Current Knowledge and Future Perspectives

Gamma-delta [γδ] T cells are a significant subset of T cells with ability to recognize many antigens without the guidance of major histocompatibility complex (MHC) molecules. A lot of studies have been conducted on them ever since they were discovered 36 years ago. Advances have been made about their structure and function. Thus, there is a need for an up-to-date review about their significance as well as their roles in Multiple Sclerosis. The study aimed to provide an up-to-date knowledge concerning gamma delta T cells in pathogenesis of Multiple Sclerosis (MS). A systematic review methodology was used to scope information from recent studies about gamma delta T cells. The review was carried out in PubMed database and it followed the PRISMA guidelines. The computerized review yielded 60 peer-reviewed articles published between 2011 and 2020. The results showed that gamma delta cells play a critical role in protection against infections and the fight against malignant cells. Most of the reviewed studies highlighted recent advances in research. It was noted that the subset of T cells plays a role in pathogenesis of MS. Several studies have highlighted the protective and detrimental effects of γδ T cells. On the one hand, the cells contribute to the pathogenesis of MS, while, on the other hand, they also help in immunoregulation. However, there is a dearth of literature on their specific role and their mechanism of action. Therefore, further studies are needed about γδ T cells in both human and animal model studies. Based on the findings of the reviewed studies, there is great promise in the use of γδ T cells for MS immunotherapy

Ability of Local Clearance of Senescent Cells in Ipsilateral Hemisphere to Mitigate Acute Ischemic Brain Injury in Mice.

Senolytic treatment has potential therapeutic efficacy for acute ischemic stroke (AIS). However, the systemic treatment of senolytics may produce off-target side effects and a toxic profile, which affect analysis of the role of acute senescence of neuronal cells in pathogenesis of AIS. We constructed a novel lenti-INK-ATTAC viral vector to introduce INK-ATTAC genes to the ipsilateral brain and locally eliminate senescent brain cells by administering AP20187 to activate caspase-8 apoptotic cascade. In this study, we have found that acute senescence is triggered by middle cerebral artery occlusion (MCAO) surgery, particularly in astrocytes and cerebral endothelial cells (CECs). The upregulation of p16INK4a and senescence-associated secretory phenotype (SASP) factors including matrix metalloproteinase-3, interleukin-1 alpha and -6 were observed in oxygen-glucose deprivation-treated astrocytes and CECs. The systemic administration of a senolytic, ABT-263, prevented the impairment of brain activity from hypoxic brain injury in mice, and significantly improved the neurological severity score, rotarod performance, locomotor activity, and weight loss. The treatment of ABT-263 reduced senescence of astrocytes and CECs in MCAO mice. Furthermore, the localized removal of senescent cells in the injured brain through the stereotaxical injection of lenti-INK-ATTAC viruses generates neuroprotective effects, protecting against acute ischemic brain injury in mice. The content of SASP factors and mRNA level of p16INK4a in the brain tissue of MCAO mice were significantly reduced by the infection of lenti-INK-ATTAC viruses. These results indicate that local clearance of senescent brain cells is a potential therapy on AIS, and demonstrate the correlation between neuronal senescence and pathogenesis of AIS.

Endocrine Disrupting Chemicals in Polycystic Ovary Syndrome: The Relevant Role of the Theca and Granulosa Cells in the Pathogenesis of the Ovarian Dysfunction.

Polycystic ovary syndrome (PCOS) is the most common heterogeneous endocrine disorder among women of reproductive age. The pathogenesis of PCOS remains elusive; however, there is evidence suggesting the potential contribution of genetic interactions or predispositions combined with environmental factors. Among these, endocrine disrupting chemicals (EDCs) have been proposed to potentially contribute to the etiology of PCOS. Granulosa and theca cells are known to cooperate to maintain ovarian function, and any disturbance can lead to endocrine disorders, such as PCOS. This article provides a review of the recent knowledge on PCOS pathophysiology, the role of granulosa and theca cells in PCOS pathogenesis, and the evidence linking exposure to EDCs with reproductive disorders such as PCOS.

Crucial role of T cells in NAFLD-related disease: A review and prospect.

Nonalcoholic fatty liver disease (NAFLD) includes a series of hepatic manifestations, starting with liver steatosis and potentially evolving towards nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis or even hepatocellular carcinoma (HCC). Its incidence is increasing worldwide. Several factors including metabolic dysfunction, oxidative stress, lipotoxicity contribute to the liver inflammation. Several immune cell-mediated inflammatory processes are involved in NAFLD in which T cells play a crucial part in the progression of the disease. In this review, we focus on the role of different subsets of both conventional and unconventional T cells in pathogenesis of NAFLD. Factors regarding inflammation and potential therapeutic approaches targeting immune cells in NASH are also discussed.

Role of T Cells in the Pathogenesis of Rheumatoid Arthritis: Focus on Immunometabolism Dysfunctions.

Evidence demonstrated that metabolic-associated T cell abnormalities could be detected in the early stage of RA development. In this context, molecular evaluations have revealed changes in metabolic pathways, leading to the aggressive phenotype of RA T cells. A growing list of genes is downregulated or upregulated in RA T cells, and most of these genes with abnormal expression fall into the category of metabolic pathways. It has been shown that RA T cells shunt glucose towards the pentose phosphate pathway (PPP), which is associated with a high level of nicotinamide adenine dinucleotide phosphate (NADPH) and intermediate molecules. An increased level of NADPH inhibits ATM activation and thereby increases the proliferation capabilities of the RA T cells. Defects in the DNA repair nuclease MRE11A cause failures in repairing mitochondrial DNA, resulting in inhibiting the fatty acid oxidation pathway and further elevated cytoplasmic lipid droplets. Accumulated lipid droplets employ to generate lipid membranes for the cell building program and are also used to form the front-end membrane ruffles that are accomplices with invasive phenotypes of RA T cells. Metabolic pathway involvement in RA pathogenesis expands the pathogenic concept of the disease beyond the common view of autoimmunity triggered by autoantigen recognition. Increased knowledge about metabolic pathways' implications in RA pathogenesis paves the way to understand better the environment/gene interactions and host/microbiota interactions and introduce potential therapeutic approaches. This review summarized emerging data about the roles of T cells in RA pathogenesis with a focus on immunometabolism dysfunctions and how these metabolic alterations can affect the disease process.

CD4+ T-cell cooperation promoted pathogenic function of activated naïve B cells of patients with SLE

ObjectiveTo explore cooperation between activated naïve (aNAV) B cells and CD4+ T cells in the pathogenesis of SLE through autoantibody production, T-cell differentiation and inflammatory cytokine secretion.MethodsPeripheral blood mononuclear cell...

Aptamer‐Modified Nanohydrogel Microarrays for Bioselective Cancer Cell Immobilization

AbstractPhotolithography combined with surface nucleated protein self‐assembly of azido‐modified spider silk proteins is used to create an arbitrarily shaped, inherently cell repellent micropattern based on nanofibrillar networks. Using “click” chemistry with dibenzocyclooctin modified oligonucleotides, the microstructures are functionalized with DNA‐aptamers, which selectively bind cancer cell markers protein tyrosine kinase 7 or nucleolin. The epitope‐specific cell interaction on the aptamer‐modified surfaces is tested using human non‐adherend leukemia T cells (Jurkat), as well as adherent cervix carcinoma (HeLa) and neuroblastoma (Kelly) cells. The cells can be immobilized with high precision and cell densities on the pattern, also revealing spatially defined proliferation and spreading into distinct morphologies upon cultivation. The formation of integrin‐based focal adhesions occurs in the case of the aptamer immobilized cancer cells, similarly to those anchored on RGD‐modified pattern. The firm aptamer‐marker anchorage allows for the formation of integrin‐dependent cell adhesions. Due to the amenability of the recombinant spider silk protein towards chemical and genetical modifications, the presented micropatterned fibrous networks have great potential for further development of adjustable and biocompatible cell‐specific arrays, enabling applications in circulating cancer cell isolation and cultivation, studies on the cell's pathogenesis, progression and metastasis capabilities as well as enabling development of platforms for personalized medicine.

Involvement of B cells in the development of systemic sclerosis.

Systemic sclerosis (SSc) is a rare intractable systemic disease that causes fibrosis and vasculopathy against a background of autoimmune abnormalities. Although the etiology is not yet fully understood, the type of autoantibodies detected in SSc is closely associated with disease severity and prognosis, supporting that those autoimmune abnormalities play an important role in the pathogenesis of SSc. Although the direct pathogenicity of autoantibodies found in SSc is unknown, many previous studies have shown that B cells are involved in the development of SSc through a variety of functions. Furthermore, a number of clinical studies have been conducted in which B-cell depletion therapy has been tried for SSc, and many of these studies have found B-cell depletion therapy to be effective for SSc. However, the involvement of B cells in pathogenesis is complex, as they not only promote inflammation but also play an inhibitory role. This article outlines the role of B cells in the development of SSc, including the latest research.

Alteration of circulating unconventional T cells in cerebral ischemia: an observational study

Immune reactions provoked by cerebral ischemia play crucial roles in the pathogenesis of brain damage and contribute to tissue regeneration processes. While functions of many immune cell types in post-ischemic inflammation have been well studied in experimental stroke, the exact roles played by unconventional T cells in pathogenesis of the clinical stroke remain to be precisely determined. In the present study, we investigated the frequencies and absolute cell numbers of peripheral blood T lymphocyte subpopulations including those of invariant natural killer T (iNKT) cells, CD3+CD56+ NKT-like (NKTL) cells, and γδ T cells from patients with acute cerebral infarction (ACI), chronic cerebrovascular disease (CCD) or chronic cerebral circulation insufficiency (CCI) by flow cytometry, and analyzed their association with the disease severity and the clinical outcome. We observed significantly reduced cell numbers of circulating iNKT cells, NKTL cells and γδ T cells in cerebral ischemia patients as compared with the healthy controls. Of note, we also demonstrated that numbers of peripheral blood iNKT and γδ T cells are significantly reduced in patients with ACI when compared among different cerebral ischemia patient groups. Moreover, the reduced number of iNKT cells is significantly associated with the disease severity and recovery in cerebral ischemia patients. Our results demonstrate for the first time the reduction of peripheral blood NKTL, iNKT and γδ T cells in patients with the cerebral ischemia, and particularly reduced iNKT and γδ T cells in the acute phase. The reduction of iNKT cells seems to be significantly associated with the disease severity and recovery. We hope that our findings might lead to the identification of predictive and prognostic values of human peripheral unconventional T cell subsets in the cerebral ischemia.

The Role of Crosstalk of Immune Cells in Pathogenesis of Chronic Spontaneous Urticaria.

Chronic spontaneous urticaria (CSU) is defined as recurrent episodes of spontaneous wheal development and/or angioedema for more than six weeks and at least twice a week. The core link in the pathogenesis of CSU is the activation of mast cells, T cells, eosinophils, and other immune cells infiltrating around the small venules of the lesion. Increased vascular permeability, vasodilatation, and recruitment of inflammatory cells directly depend on mast cell mediators’ release. Complex regulatory systems tightly influence the critical roles of mast cells in the local microenvironment. The bias toward Th2 inflammation and autoantibodies derived from B cells, histamine expressed by basophils, and initiation of the extrinsic coagulation pathway by eosinophils or monocytes exerts powerful modulatory influences on mast cells. Cell-to-cell interactions between mast cells and eosinophils/T cells also are regulators of their function and may involve CSU’s pathomechanism. This review summarizes up-to-date knowledge regarding the crosstalk between mast cells and other immune cells, providing the impetus to develop new research concepts and treatment strategies for CSU.