Nicola Laura Diny
@uni-bonn.de
University of Bonn
RESEARCH, TEACHING, or OTHER INTERESTS
Immunology
Scopus Publications
- Editorial: Update on eosinophil-associated diseases
Nicola Laura Diny, Yoshiyuki Yamada, Nives Zimmermann
Frontiers in Allergy, 2025
Eosinophils are increasingly recognized as key players in the intestinal immune system, contributing to the antimicrobial response and immune homeostasis (5)(6)(7)(8). Their role in inflammatory bowel diseases however, remains controversial. On one hand, increased eosinophil numbers and evidence of degranulation in IBD point toward a pathologic role (9). On the other hand, evidence from animal models suggests that eosinophils may play immunoregulatory roles, dampening inflammation (10,11). The review here by Tomii and Kano highlights relevant articles on both sides, revealing a complex and likely contextdependent role for eosinophils. They further postulate the hypothesis that eosinophil-derived reactive oxygen species (ROS), particularly hydrogen peroxide, contribute to a regulatory function in maintaining intestinal barrier integrity. In this model, appropriate levels of ROS from eosinophils and other cell types promote epithelial growth, mucus secretion, and pathogen control. Excess ROS, however, which may be released during uncontrolled eosinophil activation, causes tissue damage and amplifies inflammation. The authors further propose a mechanism by which the inhibitory receptor Siglec-8 may be blocked by dietderived ligands. The relevance of these pathways for IBD pathogenesis remains to be tested experimentally.Similarly, eosinophils have been shown to have both host-protective and host-destructive roles in the respiratory tract. Sasaki et al. summarize what is known about the asthma-viral infection crosstalk of eosinophils. Briefly, in type 2 cytokine mediated airway inflammation such as asthma, eosinophils contribute to tissue injury (12)(13)(14)(15). In contrast, when activated by interferons such as in viral infections, eosinophils have antiviral actions and contribute to host protection (16,17). However, eosinophils in type 2 cytokine environments have impaired antiviral activity and patients with asthma are vulnerable to viral infections (18)(19)(20)(21) suggesting impaired eosinophil antiviral function is involved in asthma exacerbation. Another mechanism for host protective versus destructive roles of eosinophils is in the heterogeneity of eosinophils, with different subtypes and/or activation states leading to different outcomes (11,22,23). Graf et al. provide a review of eosinophil recruitment and heterogeneity during allergic airway inflammation. Particularly, in the lungs, a subset of resident eosinophils have immune regulatory and homeostatic functions. In contrast, inflammatory eosinophils which expand in allergic airway inflammation in mouse models and patients with asthma have a pro-inflammatory phenotype and function. Thus, subtypes or activation states of eosinophils may guide their homeostatic or pro-inflammatory role, and the mechanisms are being actively elucidated.Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease characterized by marked eosinophil infiltration of the esophageal epithelium, leading to symptoms such as dysphagia, vomiting, and feeding difficulties. The prevalence of EoE has risen rapidly in Western countries over the past two decades, while it remains relatively rare in Asia (24). Recent contributions have expanded the scope of knowledge from clinical observation to the discovery of biomarkers and environmental interactions. Noble et al. conducted a PRISMA-based systematic review of 37 studies (2017-2024) investigating over 80 non-invasive biomarkers for EoE, across blood, saliva, breath and urine, as well as minimally-invasive esophageal sampling techniques such as Cytosponge, EST, and brushing. While peripheral eosinophil counts have been the focus of the majority of studies, their diagnostic reliability remains limited. In contrast, eosinophil-derived proteins (EDN, MBP-1, ECP) and cytokines such as eotaxin-3 and TGF-β emerged as promising indicators. Esophageal-specific sampling correlated best with histologic activity, underscoring the feasibility of biopsy-sparing diagnostics. Sekar et al. examined the impact of aeroallergens-including pollen, mites, and molds-on EoE pathogenesis. They highlight that inhaled antigens, through epithelial barrier disruption, can activate Th2 cytokines (IL-4, IL-5, IL-13) and amplify inflammation, revealing parallels between respiratory and gastrointestinal allergic mechanisms. Seasonal variation and atopic comorbidity support a link between respiratory sensitization and EoE exacerbation. The review also notes that subcutaneous immunotherapy may improve EoE outcomes, whereas sublingual immunotherapy can occasionally induce EoE, emphasizing the need for careful therapeutic balance. Dominicus et al. present a retrospective analysis of 79 children diagnosed with EoE between 2014 and 2020. Their study revealed that 14 patients had normal appearing mucosa yet histologic evidence of EoE, emphasizing the need for additional diagnostic evaluation even in the absence of grossly visible changes. Treatment primarily included proton pump inhibitors, with adjunctive swallowed budesonide or elimination diets achieving remission in approximately 87% of cases, though relapses were common. The findings highlight the necessity for long-term monitoring and individualized management strategies. Collectively, these EoE studies shift the disease concept from a purely food-driven reaction toward a systemic, type 2 inflammation-dominant disorder influenced by genetic, epithelial, and environmental factors. The prospective integration of non-invasive biomarker assessment, environmental control, and targeted biologics holds the potential to transform EoE care into a precision medicine paradigm.Across organ systems, the studies in this Research Topic reveal the dual and contextdependent nature of eosinophils-from tissue repair and immune regulation to fibrosis and chronic inflammation. Functional heterogeneity, tissue adaptation, and the balance between activation and regulation emerge as recurring themes. Biologic therapies targeting IL-5, IL-4Rα, or Siglec-8 underscore the clinical potential of modulating eosinophil pathways but also demand robust biomarkers to predict response. Integration of omics-based profiling, imaging, and minimally invasive monitoring will be crucial to track eosinophil dynamics longitudinally. Ultimately, the collective efforts reflected here pave the way toward a mechanistic and personalized approach to eosinophil-associated diseases. - Correction: Editorial: Update on eosinophil-associated diseases (Frontiers in Allergy, (2025), 6, (1740057), 10.3389/falgy.2025.1740057)
Nicola Laura Diny, Yoshiyuki Yamada, Nives Zimmermann
Frontiers in Allergy, 2025
A correction refers to a change to their article that the author wishes to publish after publication. The publication of this article is subject to Frontiers' editorial approval.• Please read through all the templates before choosing • Pick the most relevant text template(s) from the following page and delete all others.• Edit the text as necessary, ensuring that the original incorrect text is included for the record, please see the below. • Please do not use any extra formatting when editing the templates, and only modify the red text unless absolutely necessary • Submit to Frontiers following the instructions on this page.When the original text contained incorrect information, to preserve the scientific record, please include that text when editing the below templates. For example:There was a mistake in the Funding statement, an incorrect number was used.The correct number is "2015C03Bd051.". The publisher apologizes for this mistake.The original version of this article has been updated. - Drosophila AHR limits tumor growth and stem cell proliferation in the intestine
Minghua Tsai, Jiawei Sun, Cyrille Alexandre, Michael Shapiro, Adrien Franchet, Ying Li, Alex P. Gould, Jean-Paul Vincent, Brigitta Stockinger, Nicola Laura Diny
Wellcome Open Research, 2025
Background The aryl hydrocarbon receptor (AHR) plays important roles in intestinal homeostasis, limiting tumour growth and promoting differentiation in the intestinal epithelium. Spineless, the Drosophila homolog of AHR, has only been studied in the context of development but not in the adult intestine. Methods The role of Spineless in the Drosophila midgut was studied by overexpression or inactivation of Spineless in infection and tumour models and RNA sequencing of sorted midgut progenitor cells. Results We show that spineless is upregulated in the adult intestinal epithelium after infection with Pseudomonas entomophila (P.e.). Spineless inactivation increased stem cell proliferation following infection-induced injury. Spineless overexpression limited intestinal stem cell proliferation and reduced survival after infection. In two tumour models, using either Notch RNAi or constitutively active Yorkie, Spineless suppressed tumour growth and doubled the lifespan of tumour-bearing flies. At the transcriptional level it reversed the gene expression changes induced in Yorkie tumours, counteracting cell proliferation and altered metabolism. Conclusions These findings demonstrate a new role for Spineless in the adult Drosophila midgut and highlight the evolutionarily conserved functions of AHR/Spineless in the control of proliferation and differentiation of the intestinal epithelium. - Women in STEM becoming independent: Embrace failures as part of the journey to success
Zhoujie Ding, Nicola Laura Diny, Rebecca Gentek, Shiri Gur-Cohen, Motoko Y. Kimura, Hui-Fern Koay, Giuliana Magri, Araceli Perez-Lopez, Natalia Barbara Pikor, Lauren B. Rodda
Journal of Experimental Medicine, 2024
This year at JEM, we are highlighting women in science by sharing their stories and amplifying their voices. In this Viewpoint, we hear from a cross section of women, across multiple research fields, discussing their science and the process of setting up a lab as an independent researcher. - The AHR repressor limits expression of antimicrobial genes but not AHR-dependent genes in intestinal eosinophils
Heike Weighardt, Michael Shapiro, Michelle Mayer, Irmgard Förster, Brigitta Stockinger, Nicola Laura Diny
Journal of Leukocyte Biology, 2024
Intestinal eosinophils express the aryl hydrocarbon receptor (AHR), an environmental sensor and ligand-activated transcription factor that responds to dietary or environmental ligands. AHR regulates tissue adaptation, survival, adhesion, and immune functions in intestinal eosinophils. The AHR repressor (AHRR) is itself induced by AHR and believed to limit AHR activity in a negative feedback loop. We analyzed gene expression in intestinal eosinophils from wild-type and AHRR knockout mice and found that AHRR did not suppress most AHR-dependent genes. Instead, AHRR limited the expression of a distinct small set of genes involved in the innate immune response. These included S100 proteins, antimicrobial proteins, and alpha-defensins. Using bone marrow–derived eosinophils, we found that AHRR knockout eosinophils released more reactive oxygen species upon stimulation. This work shows that the paradigm of AHRR as a repressor of AHR transcriptional activity does not apply to intestinal eosinophils. Rather, AHRR limits the expression of innate immune response and antimicrobial genes, possibly to maintain an anti-inflammatory phenotype in eosinophils when exposed to microbial signals in the intestinal environment. - Dietary environmental factors shape the immune defense against Cryptosporidium infection
Muralidhara Rao Maradana, N. Bishara Marzook, Oscar E. Diaz, Tapoka Mkandawire, Nicola Laura Diny, Ying Li, Anke Liebert, Kathleen Shah, Mauro Tolaini, Martin Kváč, Brigitta Stockinger, Adam Sateriale
Cell Host and Microbe, 2023
Cryptosporidium is a leading cause of diarrheal-related deaths in children, especially in resource-poor settings. It also targets the immunocompromised, chronically infecting people living with HIV and primary immunodeficiencies. There is no vaccine or effective treatment. Although it is known from human cases and animal models that CD4+ T cells play a role in curbing Cryptosporidium, the role of CD8+ T cells remains to be defined. Using a Cryptosporidium tyzzeri mouse model, we show that gut-resident CD8+ intraepithelial lymphocytes (IELs) confer resistance to parasite growth. CD8+ IELs express and depend on the ligand-dependent transcription factor aryl hydrocarbon receptor (AHR). AHR deficiency reduces CD8+ IELs, decreases their cytotoxicity, and worsens infection. Transfer of CD8+ IELs rescues severely immunodeficient mice from death following Cryptosporidium challenge. Finally, dietary supplementation of the AHR pro-ligand indole-3-carbinol in newborn mice promotes resistance to infection. Therefore, common dietary metabolites augment the host immune response to cryptosporidiosis, protecting against disease. - Hypereosinophilia causes progressive cardiac pathologies in mice
Nicola Laura Diny, Megan Kay Wood, Taejoon Won, Monica Vladut Talor, Clarisse Lukban, Djahida Bedja, Nadan Wang, Hannah Kalinoski, Abdel Daoud, C. Conover Talbot, Brian Leei Lin, Daniela Čiháková
Iscience, 2023
Hypereosinophilic syndrome is a progressive disease with extensive eosinophilia that results in organ damage. Cardiac pathologies are the main reason for its high mortality rate. A better understanding of the mechanisms of eosinophil-mediated tissue damage would benefit therapeutic development. Here, we describe the cardiac pathologies that developed in a mouse model of hypereosinophilic syndrome. These IL-5 transgenic mice exhibited decreased left ventricular function at a young age which worsened with age. Mechanistically, we demonstrated infiltration of activated eosinophils into the heart tissue that led to an inflammatory environment. Gene expression signatures showed tissue damage as well as repair and remodeling processes. Cardiomyocytes from IL-5Tg mice exhibited significantly reduced contractility relative to wild type (WT) controls. This impairment may result from the inflammatory stress experienced by the cardiomyocytes and suggest that dysregulation of contractility and Ca 2+ reuptake in cardiomyocytes contributes to cardiac dysfunction at the whole organ level in hypereosinophilic mice. - The aryl hydrocarbon receptor contributes to tissue adaptation of intestinal eosinophils in mice
Nicola Laura Diny, Barbora Schonfeldova, Michael Shapiro, Matthew L. Winder, Sunita Varsani-Brown, Brigitta Stockinger
Journal of Experimental Medicine, 2022
Eosinophils are potent sources of inflammatory and toxic mediators, yet they reside in large numbers in the healthy intestine without causing tissue damage. We show here that intestinal eosinophils were specifically adapted to their environment and underwent substantial transcriptomic changes. Intestinal eosinophils upregulated genes relating to the immune response, cell–cell communication, extracellular matrix remodeling, and the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor with broad functions in intestinal homeostasis. Eosinophils from AHR-deficient mice failed to fully express the intestinal gene expression program, including extracellular matrix organization and cell junction pathways. AHR-deficient eosinophils were functionally impaired in the adhesion to and degradation of extracellular matrix, were more prone to degranulation, and had an extended life span. Lack of AHR in eosinophils had wider effects on the intestinal immune system, affecting the T cell compartment in nave and helminth-infected mice. Our study demonstrates that the response to environmental triggers via AHR partially shapes tissue adaptation of eosinophils in the small intestine. - The Cardiac Microenvironment Instructs Divergent Monocyte Fates and Functions in Myocarditis
Xuezhou Hou, Guobao Chen, William Bracamonte-Baran, Hee Sun Choi, Nicola L. Diny, Jungeun Sung, David Hughes, Taejoon Won, Megan Kay Wood, Monica V. Talor, David Joel Hackam, Karin Klingel, Giovanni Davogustto, Heinrich Taegtmeyer, Isabelle Coppens, Jobert G. Barin, Daniela Čiháková
Cell Reports, 2019
MDMs are associated with the reduction of cardiac fibrosis and prevention of the myocarditis sequalae. - Sca-1 + cardiac fibroblasts promote development of heart failure
Guobao Chen, William Bracamonte‐Baran, Nicola L. Diny, Xuezhou Hou, Monica V. Talor, Kai Fu, Yue Liu, Giovanni Davogustto, Hernan Vasquez, Heinrich Taegtmeyer, O. Howard Frazier, Ari Waisman, Simon J. Conway, Fengyi Wan, Daniela Čiháková
European Journal of Immunology, 2018
The causative effect of GM‐CSF produced by cardiac fibroblasts to development of heart failure has not been shown. We identified the pathological GM‐CSF‐producing cardiac fibroblast subset and the specific deletion of IL‐17A signaling to these cells attenuated cardiac inflammation and heart failure. We describe here the CD45−CD31−CD29+mEF‐SK4+PDGFRα+Sca‐1+periostin+ (Sca‐1+) cardiac fibroblast subset as the main GM‐CSF producer in both experimental autoimmune myocarditis and myocardial infarction mouse models. Specific ablation of IL‐17A signaling to Sca‐1+periostin+ cardiac fibroblasts (PostnCreIl17rafl/fl) protected mice from post‐infarct heart failure and death. Moreover, PostnCreIl17rafl/fl mice had significantly fewer GM‐CSF‐producing Sca‐1+ cardiac fibroblasts and inflammatory Ly6Chi monocytes in the heart. Sca‐1+ cardiac fibroblasts were not only potent GM‐CSF producers, but also exhibited plasticity and switched their cytokine production profiles depending on local microenvironments. Moreover, we also found GM‐CSF‐positive cardiac fibroblasts in cardiac biopsy samples from heart failure patients of myocarditis or ischemic origin. Thus, this is the first identification of a pathological GM‐CSF‐producing cardiac fibroblast subset in human and mice hearts with myocarditis and ischemic cardiomyopathy. Sca‐1+ cardiac fibroblasts direct the type of immune cells infiltrating the heart during cardiac inflammation and drive the development of heart failure. - Whi2 is a conserved negative regulator of TORC1 in response to low amino acids
Xianghui Chen, Guiqin Wang, Yu Zhang, Margaret Dayhoff-Brannigan, Nicola L. Diny, Mingjun Zhao, Ge He, Cierra N. Sing, Kyle A. Metz, Zachary D. Stolp, Abdel Aouacheria, Wen-Chih Cheng, J. Marie Hardwick, Xinchen Teng
Plos Genetics, 2018 - Regulation of autoimmune myocarditis by host responses to the microbiome
Jobert G. Barin, Monica V. Talor, Nicola L. Diny, SuFey Ong, Julie A. Schaub, Elizabeth Gebremariam, Djahida Bedja, Guobao Chen, Hee Sun Choi, Xuezhou Hou, Lei Wu, Ashley B. Cardamone, Daniel A. Peterson, Noel R. Rose, Daniela Čiháková
Experimental and Molecular Pathology, 2017 - Eosinophils in autoimmune diseases
Nicola L. Diny, Noel R. Rose, Daniela Čiháková
Frontiers in Immunology, 2017 - Eosinophil-derived IL-4 drives progression of myocarditis to inflammatory dilated cardiomyopathy
Nicola L. Diny, G. Christian Baldeviano, Monica V. Talor, Jobert G. Barin, SuFey Ong, Djahida Bedja, Allison G. Hays, Nisha A. Gilotra, Isabelle Coppens, Noel R. Rose, Daniela Čiháková
Journal of Experimental Medicine, 2017 - Macrophages and cardiac fibroblasts are the main producers of eotaxins and regulate eosinophil trafficking to the heart
Nicola L. Diny, Xuezhou Hou, Jobert G. Barin, Guobao Chen, Monica V. Talor, Julie Schaub, Stuart D. Russell, Karin Klingel, Noel R. Rose, Daniela Čiháková
European Journal of Immunology, 2016 - Collaborative Interferon-γ and Interleukin-17 Signaling Protects the Oral Mucosa from Staphylococcus aureus
Jobert G. Barin, Monica V. Talor, Julie A. Schaub, Nicola L. Diny, Xuezhou Hou, Matthew Hoyer, Nathan K. Archer, Elizabeth S. Gebremariam, Meghan F. Davis, Lloyd S. Miller, Noel R. Rose, Daniela Čiháková
American Journal of Pathology, 2016 - Pathogenic IL-23 signaling is required to initiate GM-CSF-driven autoimmune myocarditis in mice
Lei Wu, Nicola L. Diny, SuFey Ong, Jobert G. Barin, Xuezhou Hou, Noel R. Rose, Monica V. Talor, Daniela Čiháková
European Journal of Immunology, 2016 - Natural killer cells limit cardiac inflammation and fibrosis by halting eosinophil infiltration
SuFey Ong, Davinna L. Ligons, Jobert G. Barin, Lei Wu, Monica V. Talor, Nicola Diny, Jillian A. Fontes, Elizabeth Gebremariam, David A. Kass, Noel R. Rose, Daniela Čiháková
American Journal of Pathology, 2015 - Ubiquitin-like protein ISG15 (Interferon-Stimulated Gene of 15 kDa) in host defense against heart failure in a mouse model of virus-induced cardiomyopathy
Anna Rahnefeld, Karin Klingel, Anett Schuermann, Nicola L. Diny, Nadine Althof, Anika Lindner, Philipp Bleienheuft, Konstantinos Savvatis, Dorota Respondek, Elisa Opitz, Lars Ketscher, Martina Sauter, Ulrike Seifert, Carsten Tschöpe, Wolfgang Poller, Klaus-Peter Knobeloch, Antje Voigt
Circulation, 2014 - Genome-wide consequences of deleting any single gene
Xinchen Teng, Margaret Dayhoff-Brannigan, Wen-Chih Cheng, Catherine E. Gilbert, Cierra N. Sing, Nicola L. Diny, Sarah J. Wheelan, Maitreya J. Dunham, Jef D. Boeke, Fernando J. Pineda, J. Marie Hardwick
Molecular Cell, 2013
