Review
Respiratory System
Amy M. de Waal, Pieter S. Hiemstra, Tom H. M. Ottenhoff, Simone A. Joosten, Anne M. van der Does
Summary: The lung epithelium plays a crucial role in tuberculosis disease, acting as a barrier to Mycobacterium tuberculosis and responding to infection by producing immune mediators. The interactions between epithelial cells, immune cells, and Mtb are important for understanding the early events of Mtb infection.
Article
Immunology
Xin Lei, Jara Palomero, Iris de Rink, Tom de Wit, Martijn van Baalen, Yanling Xiao, Jannie Borst
Summary: This study reveals that Flagellin can recruit circulating M phi/OC progenitors into infected tissues through the TLR5 axis, which then stimulates these progenitors to differentiate locally into M phi s. This novel finding suggests that this pathway may enhance host protection against bacterial infection at mucosal sites, in addition to monocyte recruitment.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Xiao-Yue Chen, Ching Kao, Syue-Wei Peng, Jer-Hwa Chang, Yueh-Lun Lee, Vincent Laiman, Kian Fan Chung, Pankaj K. Bhavsar, Didik Setyo Heriyanto, Kai-Jen Chuang, Hsiao-Chi Chuang
Summary: This study investigated the role of the DCLK1/Hippo pathway in mediating AECII differentiation in ARDS. The results showed that LPS can induce AECII differentiation by reducing the expression of SPC and p53 while increasing the expression of T1 alpha and E-cadherin. Nuclear YAP dynamic regulation and increased TAZ levels were also observed in LPS-exposed AECII. Moreover, DCLK1 expression was found to be reduced in isolated human AECII of ARDS, consistent with the results in LPS-exposed AECII and mouse SPC-positive cells. The study concludes that the DCLK1/Hippo pathway could be a potential therapeutic target in patients with ARDS.
MOLECULAR MEDICINE
(2023)
Article
Cell Biology
Ilena Vincenti, Nicolas Page, Karin Steinbach, Alexander Yermanos, Sylvain Lemeille, Nicolas Nunez, Mario Kreutzfeldt, Bogna Klimek, Giovanni Di Liberto, Kristof Egervari, Margot Piccinno, Ghazal Shammas, Alexandre Mariotte, Nicolas Fonta, Nicolas Liaudet, Danielle Shlesinger, Anna Rita Liuzzi, Ingrid Wagner, Cynthia Saadi, Christine Stadelmann, Sai Reddy, Burkhard Becher, Doron Merkler
Summary: The study reveals that tissue-resident memory T cells (T-RM) may initiate CNS inflammation and immunopathology in chronic inflammatory diseases of the central nervous system (CNS), independent of circulating CD8(+) T cells. In the absence of CD4(+) T cells, CD8(+) T cells fail to expand and differentiate into terminal effectors. This sheds light on why inflammatory processes may evade current immunomodulatory treatments in chronic autoimmune CNS conditions.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Cell Biology
Rong Xu, Laura C. Jacques, Shadia Khandaker, Miguel Leon-Rios, Daan Beentjes, Xiaoqing Wei, Neil French, Daniel R. Neill, Aras Kadioglu
Summary: Streptococcus pneumoniae is a highly morbid and mortal pathogen. Activation of pulmonary Treg cells with upregulated TNFR2 expression occurs upon pneumococcal infection. Deficiency in TNFR2 compromises Treg cell responses, leading to highly activated IL-17A-producing y8 T cell responses and increased susceptibility to disease. Blocking IL-17A at early stage of infection improves survival in TNFR2-deficient mice.
Article
Pharmacology & Pharmacy
Haixiong Tang, Zemin Chen, Sudan Gan, Yan Liang, Hailing Zhang, Changyun Yang, Liqin Lin, Yubiao Guo, Shiyue Li, Jing Li, Lihong Yao
Summary: This study demonstrates the crucial role of glucose transporter 1 (GLUT1) in the dysfunction of epithelial tight junctions during the development of acute lung injury (ALI).
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Immunology
Carlos A. Alvarez, Emily Qian, Leandre M. Glendenning, Kalob M. Reynero, Emily N. Kukan, Brian A. Cobb
Summary: Asthma, a chronic inflammatory disease characterized by leukocyte infiltration and tissue remodeling, is associated with increased glycan fucosylation in airway epithelial cells. This modification is important for the recruitment of eosinophils and neutrophils.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Respiratory System
Kirsty L. Bradley, Clare A. Stokes, Stefan J. Marciniak, Lisa C. Parker, Alison M. Condliffe
Summary: The lungs are exposed to various environmental toxins and pathogens, leading to respiratory diseases associated with hypoxia. Endoplasmic reticulum stress can be triggered by these factors, activating the unfolded protein response. This response plays a significant role in the pathogenesis and progression of respiratory diseases, making it a potential target for therapeutic interventions.
Article
Physiology
Emily R. Siegel, Roxanne H. Croze, Xiaohui Fang, Michael A. Matthay, Jeffrey E. Gotts
Summary: This experimental study highlights the important role of endogenous specialized proresolving mediators (SPMs) such as LXA4 and RvD1 in resolving lung injury caused by pneumococcal pneumonia. The mechanism of their benefits includes enhancing bacterial clearance and reducing pulmonary edema by restoring lung alveolar-capillary barrier permeability.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2021)
Article
Cell Biology
Prajakta Shinde, Alexander Kiepas, Lei Zhang, Shreya Sudhir, Konstantinos Konstantopoulos, Nicholas M. Stamatos
Summary: Polysialic acid (polySia) is a post-translational modification of cell-surface proteins that plays a role in cellular interactions. In a study using mice deficient in polySia infected with Streptococcus pneumoniae (Spn), it was found that these mice were less susceptible to infection and cleared the bacteria faster. However, their lung infiltration of immune cells was diminished, possibly due to dysregulated signaling. The loss of polySia from migrating immune cells in infected wild-type mice suggests its changing role during an immune response.
Article
Biochemistry & Molecular Biology
Magali Humbert, Kristina Seiler, Severin Mosimann, Vreni Rentsch, Katyayani Sharma, Amit Pandey, Sharon L. McKenna, Mario P. Tschan
Summary: The study found that FASN mRNA levels were significantly higher in acute myeloid leukemia (AML) patients compared to healthy granulocytes or hematopoietic progenitors. Inhibition of FASN expression levels accelerated differentiation of APL cell lines and re-sensitized ATRA refractory non-APL AML cells. FASN reduction promoted translocation of transcription factor EB (TFEB) to the nucleus, leading to activation of CLEAR network genes and lysosomal biogenesis.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Biochemistry & Molecular Biology
Rene Roy, Ayed Allawzi, Nana Burns, Christina Sul, Victoria Rubio, Jessica Graham, Kurt Stenmark, Eva Nozik, Rubin Tuder, Christine Vohwinkel
Summary: This study reveals that lactate produced by alveolar type II cells (ATII) in acute lung injury (ALI) can shift alveolar macrophages (AM) towards an anti-inflammatory phenotype, thereby mitigating excessive inflammation.
Article
Biotechnology & Applied Microbiology
Mandi M. M. Roe, Taylor Do, Sean Turner, Allison M. M. Jevitt, Magdalena Chlebicz, Karley White, Antonius G. P. Oomens, Susannah Rankin, Susan Kovats, Heather Gappa-Fahlenkamp
Summary: Researchers developed a 3D human tissue-engineered lung model (3D-HTLM) that mimics the cellular complexity of the lower airway. This model allows studying the immune response to respiratory infections by incorporating different cell types.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Immunology
Nozomi Sakakibara, Paul E. Clavijo, Cem Sievers, Veronica C. Gray, Kathryn E. King, Andrea L. George, Roshini M. Ponnamperuma, Beatriz A. Walter, Zhong Chen, Carter Van Waes, Clint T. Allen, Wendy C. Weinberg
Summary: This study established an immune competent mouse model to evaluate the immune suppressive role of ?Np63a and HRAS in the tumor microenvironment. Orthotopic grafting of keratinocytes overexpressing ?Np63a and HRAS resulted in the recruitment of immunosuppressive PMN-MDSCs cells and the development of an immunosuppressive tumor microenvironment.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Hematology
Zhi Wen, Grant Yun, Alexander Hebert, Guangyao Kong, Erik A. Ranheim, Remington Finn, Adhithi Rajagoplan, Shuyi Li, Yun Zhou, Mei Yu, Alisa Damnernsawad, Jeroen P. Roose, Joshua J. Coon, Renren Wen, Demin Wang, Jing Zhang
Summary: ETP-ALL is characterized by hyperactivation of cytokine receptor/Ras signaling, with downregulation of WT KRAS and Rasgrp1 serving as negative regulators of Ras/ERK pathway, contributing to cell proliferation in oncogenic Nras-driven ETP-like leukemia.
Article
Gastroenterology & Hepatology
Moritz Leppkes, Aylin Lindemann, Stefanie Goesswein, Susanne Paulus, Dominik Roth, Anne Hartung, Eva Liebing, Sebastian Zundler, Miguel Gonzalez-Acera, Jay Patankar, Fabrizio Mascia, Kristina Scheibe, Markus Hoffmann, Stefan Uderhardt, Christine Schauer, Sebastian Foersch, Clemens Neufert, Michael Vieth, Georg Schett, Raja Atreya, Anja A. Kuehl, Andre Bleich, Christoph Becker, Martin Herrmann, Markus F. Neurath
Summary: Bleeding ulcers and erosions are common in active ulcerative colitis, with fibrin layers correlated with rectal bleeding. Neutrophils induce secondary immunothrombosis through PAD4-dependent mechanisms, protecting against acute colitis and rectal bleeding. Deficiency in immunothrombosis can lead to exacerbated colitis and increased bleeding.
Review
Gastroenterology & Hepatology
Laura Golusda, Anja A. Kuehl, Britta Siegmund, Daniela Paclik
Summary: This review discusses the influence of pain medication on inflammatory bowel disease research in colitis models, arguing that the current administration of pain medication impacts results and reproducibility, leading to misconceptions.
INFLAMMATORY BOWEL DISEASES
(2022)
Article
Immunology
Jonas Ahlers, Andrej Mantei, Laura Lozza, Manuela Staeber, Frederik Heinrich, Petra Bacher, Thordis Hohnstein, Lutz Menzel, Simge G. Yuez, Daniel Alvarez-Simon, Anne Rieke Bickenbach, Carl Weidinger, Nadine Mockel-Tenbrinck, Anja A. Kuehl, Britta Siegmund, Jochen Maul, Christian Neumann, Alexander Scheffold
Summary: We identified a Notch/STAT3-Blimp-1/c-Maf axis as a common anti-inflammatory pathway in human CD4(+) T cells and found that this pathway is defective in inflammatory bowel disease.
MUCOSAL IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Paula Zwicker, Johannes Schleusener, Silke B. Lohan, Loris Busch, Claudia Sicher, Sven Einfeldt, Michael Kneissl, Anja A. Kuhl, Cornelia M. Keck, Christian Witzel, Axel Kramer, Martina C. Meinke
Summary: A newly developed UVC LED source with a wavelength of 233 nm has been proven to be effective in bactericidal and well-tolerated on the skin. The study analyzed the bactericidal efficacy qualitatively and quantitatively using different bacterial strains and soil loads. It also assessed the compatibility of the radiation doses on skin models and compared it to UVC radiation from discharge lamps and UVB radiation. The results showed high bactericidal efficacy with minimal skin damage and low radical formation.
SCIENTIFIC REPORTS
(2022)
Article
Immunology
Justus Ninnemann, Caroline Winsauer, Marina Bondareva, Anja A. Kuehl, Laura Lozza, Pawel Durek, Donata Lissner, Britta Siegmund, Stefan H. E. Kaufmann, Mir-Farzin Mashreghi, Sergei A. Nedospasov, Andrey A. Kruglov
Summary: Successful treatment of chronic inflammatory diseases requires both the cessation of inflammation and the promotion of tissue repair. Targeting tumor necrosis factor (TNF) can induce tissue repair in inflammatory bowel disease (IBD) patients, but the underlying molecular mechanisms have been unclear. Using an experimental colitis model, this study found that TNF interferes with tissue repair by inducing a soluble antagonist of IL-22. Furthermore, membrane-bound TNF expressed by T cells perpetuates colonic inflammation, while soluble TNF produced by epithelial cells inhibits colonic epithelial repair.
MUCOSAL IMMUNOLOGY
(2022)
Article
Immunology
Ivet A. Yordanova, Karsten Juerchott, Svenja Steinfelder, Katrin Vogt, Ulrike Krueger, Anja A. Kuehl, Birgit Sawitzki, Susanne Hartmann
Summary: Intestinal parasitic nematodes can elicit prominent effector Th2-driven host immune responses, but not all infected hosts develop protection against reinfection. Nematode-cured mice harbor memory Th2 cells in both lymphoid and non-lymphoid organs, with particularly prominent expansion and strong parasite-specific Th2 responses observed in peritoneal memory Th2 cells during early recall responses.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell & Tissue Engineering
Mohammad R. Saghari Fard, Jan Philipp Krueger, Stefan Stich, Phil Berger, Anja A. Kuehl, Michael Sittinger, Tony Hartwig, Michaela Endres
Summary: In this study, PGA-HA scaffolds were used to repair annulus fibrosus defects in sheep models. The treated group showed significantly enhanced repair tissue structure compared to the untreated group, indicating the potential of PGA-HA scaffolds in supporting annulus fibrosus repair.
TISSUE ENGINEERING AND REGENERATIVE MEDICINE
(2022)
Article
Physiology
Laura Golusda, Anja A. Kuehl, Malte Lehmann, Katja Dahlke, Susanne Mueller, Philipp Boehm-Sturm, Jessica Saatz, Heike Traub, Joerg Schnorr, Christian Freise, Matthias Taupitz, Karina Biskup, Veronique Blanchard, Oliver Klein, Ingolf Sack, Britta Siegmund, Daniela Paclik
Summary: Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are characterized by chronic inflammation of the gastrointestinal tract. This study utilized very small superparamagnetic iron oxide nanoparticles (VSOPs) in magnetic resonance imaging (MRI) to detect intestinal inflammation in mouse models. The results suggest that VSOPs can serve as a potential contrast agent for early non-invasive diagnosis of IBD, depending on the hyaluronic acid content.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Oncology
J. J. Staudacher, Alexander Arnold, A. A. Kuehl, M. Poetzsch, S. Daum, M. Winterfeld, E. Berg, M. Hummel, B. Rau, U. Stein, C. Treese
Summary: This study aimed to investigate the prognostic role of activin tumor protein expression in esophageal and gastric adenocarcinomas. The results showed that higher levels of activin subunits were associated with lower cancer stage and longer overall survival. Furthermore, tumors with higher activin subunit expression also had higher CD4(+) T-cell infiltration, and the longer overall survival effect was only observed in tumors with high CD4(+) T-cell infiltration.
Article
Immunology
Lucia Minarrieta, Gloria J. Godoy, Lis N. Velazquez, Peyman Ghorbani, Tim Sparwasser, Luciana Berod
Summary: The CD11c(+)MHCII(+) compartment in GM-CSF cultures contains two populations with different metabolic profiles: MHCII(low)CD11b(high) cells (GM-Macs) and MHCII(high)CD11b(int) cells (GM-DCs). GM-Macs upregulate iNOS and produce nitric oxide (NO) to inhibit mitochondrial respiration (OXPHOS), while promoting glycolytic metabolism in GM-DCs, which do not express iNOS naturally.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Immunology
Ping Shen, Madlen Rother, Ulrik Stervbo, Vicky Lampropoulou, Elisabeth Calderon-Gomez, Toralf Roch, Ellen Hilgenberg, Steffi Ries, Anja A. Kuehl, Luc Jouneau, Pierre Boudinot, Simon Fillatreau
Summary: This study demonstrates the critical role of neutrophils in the regulation of antigen-specific CD4(+) T cell expansion in lymph nodes, and the counter-regulatory role of TLR signaling in this process.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Immunology
Kristina Koop, Karin Enderle, Miriam Hillmann, Laura Ruspeckhofer, Michael Vieth, Gregor Sturm, Zlatko Trajanoski, Anja A. Kuehl, Raja Atreya, Moritz Leppkes, Patrick Baum, Janine Roy, Andrea Martin, Markus F. Neurath, Clemens Neufert
Summary: Fibrostenotic disease is a common complication in Crohn's disease characterized by ECM accumulation. This study found that MMP13 expression is regulated by IL36R signaling during intestinal fibrosis, and the loss of MMP13 can alleviate intestinal fibrosis in mice. Targeting IL36R-inducible MMP13 could be a promising approach to interfere with the development and progression of intestinal fibrosis.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Nutrition & Dietetics
Janine Buettner, Elisabeth Bluethner, Sophie Greif, Anja Kuehl, Sefer Elezkurtaj, Jan Ulrich, Sebastian Maasberg, Christoph Jochum, Frank Tacke, Ulrich-Frank Pape
Summary: This study investigated biomarkers for the regulation mechanisms in the intestinal barrier during adaptive response or treatment with the glucagon-like peptide-2 analog in short bowel syndrome patients. Gene expression analyses and intestinal permeability testing were conducted. The results showed altered gene expression in nutrient transport genes and the usefulness of mannitol recovery in describing gut absorptive capacity.
Article
Biochemistry & Molecular Biology
Leonie Wittner, Lukas Wagener, Jakob J. Wiese, Iris Stolzer, Susanne M. Krug, Elisabeth Naschberger, Rene Jackstadt, Rudi Beyaert, Raja Atreya, Anja A. Kuehl, Gregor Sturm, Miguel Gonzalez-Acera, Jay V. Patankar, Christoph Becker, Britta Siegmund, Zlatko Trajanoski, Beate Winner, Markus F. Neurath, Michael Schumann, Claudia Guenther
Summary: The paracaspase MALT1 plays a crucial role in mucosal inflammation. It is highly expressed in colonic epithelial cells of UC patients and experimental colitis. Mechanistically, MALT1 protease function inhibits ferroptosis and contributes to NF-kappa B signaling and STAT3 signaling, which are involved in inflammation and tissue healing.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Koen Venken, Tine Decruy, Tim Sparwasser, Dirk Elewaut
Summary: Regulatory T cells (Tregs) and invariant natural killer T (iNKT) cells play a crucial role in controlling autoimmune diseases. The study reveals that Treg depletion enhances iNKT cell responses and leads to severe liver and gut pathology in preclinical models of autoimmunity.