Marvin Nüsken, Fabian Heinemeier, Silke Sabina Matzke, Patryk Porebski, Susann Forkel, Prasad Dasari, Andrea Braun, Andreas Erich Zautner, Michael Peter Schön, Timo Buhl
{"title":"Immune response to topical sodium lauryl sulfate differs from classical irritant and allergic contact dermatitis","authors":"Marvin Nüsken, Fabian Heinemeier, Silke Sabina Matzke, Patryk Porebski, Susann Forkel, Prasad Dasari, Andrea Braun, Andreas Erich Zautner, Michael Peter Schön, Timo Buhl","doi":"10.1002/eji.202350798","DOIUrl":"10.1002/eji.202350798","url":null,"abstract":"<p>Sodium lauryl sulfate (SLS) is used as a control irritant in patch testing for allergic contact dermatitis (ACD). However, up to 20% of those tested react to SLS, whereby the pathophysiological basis of this reaction is still unclear. To mimic patch test reactions, we repeatedly applied SLS to the skin of wild-type mice. Reactions were compared with those in a classical ACD model induced by oxazolone and an irritant contact dermatitis (ICD) model induced by croton oil. Skin inflammation was assessed with ear thickness measurements, immunohistochemistry, qRT-PCR, and flow cytometry. Topical SLS treatment was further investigated in <i>Flg/Hrnr</i><sup>−/−</sup>, <i>Myd88/Tlr3</i><sup>−/−</sup>, and <i>Rag1</i><sup>−/−</sup> mouse models. All three compounds caused ear swelling with different courses. Oxazolone treatment, compared with the ICD model, resulted in a greater influx of immune cells (CD4<sup>+</sup>, MHCII<sup>+</sup>, CD11b<sup>+</sup>). Similarly, SLS did not induce immune cell infiltration or expression of selected inflammatory and regulatory cytokines. SLS induced the most pronounced keratinocyte proliferation. Compared with wild-type mice, topical SLS application did not increase ear swelling in skin barrier deficient <i>Flg/Hrnr</i><sup>−/−</sup> mice, but led to significantly delayed swelling in mice with defects in innate or adaptive immune functions (<i>Myd88/Tlr3</i><sup>−/−</sup>, <i>Rag1</i><sup>−/−</sup>). SLS-induced contact dermatitis differed from classical ACD and ICD, as it elicited less pronounced immune alterations. Skin barrier impairment does not affect SLS-induced contact dermatitis, whereas both innate and adaptive components are involved in SLS skin reactions.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"2024 German Society for Immunology Prizes.","authors":"","doi":"10.1002/eji.202451593","DOIUrl":"https://doi.org/10.1002/eji.202451593","url":null,"abstract":"","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e2451593"},"PeriodicalIF":4.5,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The macrophage migration inhibitory factor/CD74 axis in traumatic spinal cord injury: lessons learned from animal and human studies","authors":"Serina Rubio, Veerle Somers, Judith Fraussen","doi":"10.1002/eji.202451333","DOIUrl":"10.1002/eji.202451333","url":null,"abstract":"<p>Traumatic spinal cord injury (SCI) is a severe condition leading to long-term impairment of motor, sensory, and autonomic functions. Following the initial injury, a series of additional events is initiated further damaging the spinal cord. During this secondary injury phase, both an inflammatory and immune modulatory response are triggered that have damaging and anti-inflammatory properties, respectively. The proinflammatory cytokine macrophage migration inhibitory factor (MIF) and its receptor CD74 have been extensively studied in traumatic SCI. MIF expression is increased in spinal cord tissue after experimental SCI, mainly in astrocytes and microglia, as well as in the plasma of SCI patients. Functionally, MIF and CD74 were shown to regulate astrocyte viability, proliferation and cholesterol metabolism, microglia migration, and neuronal viability. Moreover, inhibition of the MIF/CD74 axis improved the functional recovery of SCI animals. We provide a detailed overview of studies analyzing the role of MIF and CD74 in traumatic SCI. We describe results from animal studies, using rat and mouse models for SCI, and human studies. Furthermore, we propose a new path for investigation, focused on B cells, that might lead to a better understanding of how MIF and CD74 contribute to the secondary injury cascade following traumatic SCI.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451333","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mingjun Shi, Tianqi Dong, Jiaming Lin, Liu Huang, Huixia Zhang, Shuguo Sun
{"title":"Characterizing dynamic tumor–immune interactions in lung adenocarcinoma through orthotopic allograft modeling","authors":"Mingjun Shi, Tianqi Dong, Jiaming Lin, Liu Huang, Huixia Zhang, Shuguo Sun","doi":"10.1002/eji.202451342","DOIUrl":"10.1002/eji.202451342","url":null,"abstract":"<p>The major clinical challenge in lung cancer immunotherapy is drug resistance. Therefore, establishing efficient orthotopic lung cancer mouse models to explore the mechanisms of drug immunotherapy resistance is highly important. In this study, we generated multiple fluorescently labeled lung adenocarcinoma cell lines from a genetically engineered <i>KPZ</i> mice model. Orthotopic transplantation of the primary 1F3 cell line induced a strong immune response, causing many small tumors to disappear, but some tumors evaded the immune attack and eventually formed large tumors. Tumor microenvironment analysis demonstrated that M2 macrophages play key roles in the immune response. Further mechanistic studies revealed that the chemokine CCL7 promoted the infiltration of M2 macrophages to facilitate immune escape, thereby promoting tumor growth in the orthotopic mouse model. Moreover, CCL7 levels were elevated in human lung cancer biopsies and positively correlated with M2 macrophage infiltration, and high CCL7 levels predicted advanced pathological stage and poor survival in lung cancer patients. Overall, we established a visualized and orthotopic mouse model with fluorescently labeled cells to better dissect the tumor microenvironment of lung cancer and define the critical role of CCL7 in promoting M2 macrophage polarization and tumorigenesis, providing new preclinical tools and potential targets for lung cancer immunotherapy.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stefanie Dietz, Janine Hebel, Jessica Rühle, Alisha Huff, Holger K. Eltzschig, Trim Lajqi, Christian F. Poets, Christian Gille, Natascha Köstlin-Gille
{"title":"Impact of the adenosine receptor A2BR expressed on myeloid cells on immune regulation during pregnancy","authors":"Stefanie Dietz, Janine Hebel, Jessica Rühle, Alisha Huff, Holger K. Eltzschig, Trim Lajqi, Christian F. Poets, Christian Gille, Natascha Köstlin-Gille","doi":"10.1002/eji.202451149","DOIUrl":"10.1002/eji.202451149","url":null,"abstract":"<p>During pregnancy, the maternal immune system must carefully balance protection against pathogens with tolerance toward the semiallogeneic fetus. Dysfunctions of the immune system can lead to severe complications such as preeclampsia, fetal growth restriction, or pregnancy loss. Adenosine plays a role in physiological processes and plasma-level increase during pregnancy. The adenosine receptor A2B (A2BR), which is expressed on both, immune and nonimmune cells, is activated by high adenosine concentrations, achieved during pregnancy. We investigated the impact of A2BR expressed on myeloid cells on immune regulation during pregnancy using a mouse model with myeloid deficiency for A2BR. We demonstrate systemic changes in myeloid and lymphoid cell populations during pregnancy in A2BR-KO (Adora2B923<sup>f/f</sup>-LysM<sup>Cre</sup>) mice with increased monocytes, neutrophils, and T cells but decreased B cells as well as altered T-cell subpopulations with decreased Th1 cells and Tregs and increased Th17 cells. Lack of A2BR on myeloid cells caused an increased systemic expression of IL-6 but decreased systemic accumulation and function of MDSC and reduced numbers of uterine natural killer cells. The pregnancy outcome was only marginally affected. Our results demonstrate that A2BR on myeloid cells plays a role in immune regulation during pregnancy, but the clinical impact on pregnancy remains unclear.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jian Zheng, Jun Xiao, Yatong Fan, Honggang Zheng, Hongyu Liu, Jie Xiang, Lei Hai, Yan Wang, Xuejun Zhang
{"title":"CD24 regulates liver immune response and ameliorates acute hepatic injury through controlling hepatic macrophages","authors":"Jian Zheng, Jun Xiao, Yatong Fan, Honggang Zheng, Hongyu Liu, Jie Xiang, Lei Hai, Yan Wang, Xuejun Zhang","doi":"10.1002/eji.202451178","DOIUrl":"10.1002/eji.202451178","url":null,"abstract":"<p>Liver injury releases danger-associated molecular patterns, which trigger the immune response. CD24 negatively regulates the immune response by binding with danger-associated molecular patterns, but the specific role of CD24 in modulating macrophage-related inflammation during liver injury remains largely unexplored. Here, we aimed to investigate the mechanisms of macrophage CD24 in the development of liver injury. Our results show that CD24 expression is upregulated primarily in hepatic macrophages (HMs) during acute liver injury. CD24-deficient mice exhibited more severe liver injury and showed a significantly higher frequency and number of HMs, particularly Ly6C<sup>hi</sup> monocyte-derived macrophages. Mechanistically, the CD24-Siglec-G interaction plays a vital role in mitigating acute liver injury. CD24-mediated inhibitory signaling in HMs primarily limits downstream NF-κB and p38 MAPK activation through the recruitment of SHP1. Our work unveils the critical role of macrophage CD24 in negatively regulating innate immune responses and protecting against acute liver injury, thus providing potential therapeutic targets for liver-associated diseases.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lennart Riemann, Leonie M. Weskamm, Leonie Mayer, Ivan Odak, Swantje Hammerschmidt, Inga Sandrock, Michaela Friedrichsen, Inga Ravens, Janina Fuss, Gesine Hansen, Marylyn M. Addo, Reinhold Förster
{"title":"Blood transcriptome profiling reveals distinct gene networks induced by mRNA vaccination against COVID-19","authors":"Lennart Riemann, Leonie M. Weskamm, Leonie Mayer, Ivan Odak, Swantje Hammerschmidt, Inga Sandrock, Michaela Friedrichsen, Inga Ravens, Janina Fuss, Gesine Hansen, Marylyn M. Addo, Reinhold Förster","doi":"10.1002/eji.202451236","DOIUrl":"10.1002/eji.202451236","url":null,"abstract":"<p>Messenger RNA (mRNA) vaccines represent a new class of vaccines that has been shown to be highly effective during the COVID-19 pandemic and that holds great potential for other preventative and therapeutic applications. While it is known that the transcriptional activity of various genes is altered following mRNA vaccination, identifying and studying gene networks could reveal important scientific insights that might inform future vaccine designs. In this study, we conducted an in-depth weighted gene correlation network analysis of the blood transcriptome before and 24 h after the second and third vaccination with licensed mRNA vaccines against COVID-19 in humans, following a prime vaccination with either mRNA or ChAdOx1 vaccines. Utilizing this unsupervised gene network analysis approach, we identified distinct modular networks of co-varying genes characterized by either an expressional up- or downregulation in response to vaccination. Downregulated networks were associated with cell metabolic processes and regulation of transcription factors, while upregulated networks were associated with myeloid differentiation, antigen presentation, and antiviral, interferon-driven pathways. Within this interferon-associated network, we identified highly connected hub genes such as <i>STAT2</i> and <i>RIGI</i> and associated upstream transcription factors, potentially playing important regulatory roles in the vaccine-induced immune response. The expression profile of this network significantly correlated with S1-specific IgG levels at the follow-up visit in vaccinated individuals. Those findings could be corroborated in a second, independent cohort of mRNA vaccine recipients. Collectively, results from this modular gene network analysis enhance the understanding of mRNA vaccines from a systems immunology perspective. Influencing specific gene networks could lead to optimized vaccines that elicit augmented vaccine responses.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 11","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451236","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marius Piepke, Alina Jander, Nicola Gagliani, Mathias Gelderblom
{"title":"IL-17A-producing γδ T cells: A novel target in stroke immunotherapy","authors":"Marius Piepke, Alina Jander, Nicola Gagliani, Mathias Gelderblom","doi":"10.1002/eji.202451067","DOIUrl":"10.1002/eji.202451067","url":null,"abstract":"<p>The activation of the immune system is crucial for the fate of the ischemic brain tissue and neurological outcome in experimental stroke. Rapidly after stroke γδ (γδ17), T cells release IL-17A in the ischemic brain and thereby amplify the early detrimental immune response. Notably, IL-17A levels in γδ17 T cells are modulated by the intestinal microbiota which is, in turn, shaped by the diet. Importantly, besides their proinflammatory effects, meningeal γδ17 T cells have been recently implicated in regulating neuronal signaling, behavior, and cognition under homeostatic and pathological conditions at the brain–meningeal interface. Against this background, we propose that a dietary intervention represents a promising treatment option to improve poststroke outcomes by the modulation of the microbiota composition and IL-17A levels in γδ T cells.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marijn E. Snik, Noor E.I.M. Stouthamer, Joppe W. Hovius, Melissa M.J. van Gool
{"title":"Bridging the gap: Insights in the immunopathology of Lyme borreliosis","authors":"Marijn E. Snik, Noor E.I.M. Stouthamer, Joppe W. Hovius, Melissa M.J. van Gool","doi":"10.1002/eji.202451063","DOIUrl":"10.1002/eji.202451063","url":null,"abstract":"<p>Lyme borreliosis (LB), caused by <i>Borrelia burgdorferi</i> sensu lato (Bbsl) genospecies transmitted by <i>Ixodes</i> spp. ticks, is a significant public health concern in the Northern Hemisphere. This review highlights the complex interplay between Bbsl infection and host–immune responses, impacting clinical manifestations and long-term immunity. Early localized disease is characterized by erythema migrans (EM), driven by T-helper 1 (Th1) responses and proinflammatory cytokines. Dissemination to the heart and CNS can lead to Lyme carditis and neuroborreliosis respectively, orchestrated by immune cell infiltration and chemokine dysregulation. More chronic manifestations, including acrodermatitis chronica atrophicans and Lyme arthritis, involve prolonged inflammation as well as the development of autoimmunity. In addition, dysregulated immune responses impair long-term immunity, with compromised B-cell memory and antibody responses. Experimental models and clinical studies underscore the role of Th1/Th2 balance, B-cell dysfunction, and autoimmunity in LB pathogenesis. Moreover, LB-associated autoimmunity parallels mechanisms observed in other infectious and autoimmune diseases. Understanding immune dysregulation in LB provides insights into disease heterogeneity and could provide new strategies for diagnosis and treatment.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}