Review
Immunology
Eric Y. Helm, Liang Zhou
Summary: The aryl hydrocarbon receptor (Ahr) is a ligand-dependent transcription factor that plays a role in immune cell environmental sensing. It regulates the development and function of innate lymphoid cells (ILCs) and their adaptive T cell counterparts. Both ILCs and T cells share some core transcription factors and effector molecules, but they have both shared and distinct mechanisms of regulation by Ahr. This review highlights the latest findings on Ahr's transcriptional regulation of ILCs and T cells, focusing on the shared and distinct mechanisms.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Simone Sandoval, Keegan Malany, Krista Thongphanh, Clarisa A. Martinez, Michael L. Goodson, Felipe Da Costa Souza, Lo-Wei Lin, Nicolle Sweeney, Jamie Pennington, Pamela J. Lein, Nancy I. Kerkvliet, Allison K. Ehrlich
Summary: Neuropilin-1 (Nrp1), a transmembrane protein expressed on CD4(+) T cells, has been found to be highly expressed on activated effector T cells and may be involved in the identification and function of immunopathologic T cells. The downregulation of Nrp1 on CD4(+) T cells is influenced by AhR activation and IL-2. These findings suggest that Nrp1 is an activation marker for CD4(+) T cells and may play a role in AhR-mediated modulation of effector CD4(+) T cell responses.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Phuc-Tan Nguyen, Yuki Nakamura, Nguyen Quoc Vuong Tran, Kayoko Ishimaru, Thuy-An Nguyen, Yoshiaki Kobayashi, Fumie Watanabe-Saito, Tohru Okuda, Nobuhiro Nakano, Atsuhito Nakao
Summary: Ethyl caffeate (EC) is a natural phenolic compound found in medicinal plants and shows anti-allergic activity by inhibiting aryl hydrocarbon receptor (AhR) signaling. EC inhibits AhR activation and downregulates AhR target gene expressions. It also inhibits mast cell activation and IL-6 production induced by AhR ligands. These findings suggest a novel mechanism for the anti-inflammatory activity of EC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Immunology
Farooq Riaz, Fan Pan, Ping Wei
Summary: The aryl hydrocarbon receptor (AhR) is a widely studied ligand-activated transcription factor that is associated with various diseases. It regulates toxicological, biological, and cellular responses by responding to environmental toxins, dietary ligands, and allergens. Recent findings suggest that AhR also interacts with non-canonical factors to affect gene expression. AhR signaling has also been shown to have significant effects on immune cells and play a role in allergens-induced diseases.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biology
Adeline Cros, Alba De Juan, Renaud Leclere, Julio L. Sampaio, Mabel San Roman, Mathieu Maurin, Sandrine Heurtebise-Chretien, Elodie Segura
Summary: Dietary agonists of aryl hydrocarbon receptor (AhR) have a regulatory role in allergic responses, with a lack of dietary AhR ligands exacerbating cutaneous allergic responses and asthma-like allergy. Mechanistically, dietary AhR ligands regulate the inflammatory profile of epidermal cells, without affecting barrier function. These findings highlight the importance of the gut-skin axis in the development of allergic diseases.
Review
Pharmacology & Pharmacy
Ziyue Kou, Wei Dai
Summary: Aryl hydrocarbon receptor (AHR) is a cellular protein involved in detoxification of xenobiotic compounds. Research has shown that AHR plays important roles in normal development and homeostasis, and its deficiency can lead to various developmental abnormalities.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Environmental Sciences
Li Xu, Yiyun Liu, Yangsheng Chen, Ruihong Zhu, Siqi Li, Songyan Zhang, Jian Zhang, Heidi Qunhui Xie, Bin Zhao
Summary: This study found that emodin inhibits the migration ability of glioblastoma cells by activating the AhR-IL24 signaling pathway, indicating that the AhR signaling pathway can be a key target for studying the regulatory effects and mechanisms of compounds on glioblastoma migration.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2022)
Article
Cell Biology
Ana Nacarino-Palma, Eva M. Rico-Leo, Judith Campisi, Arvind Ramanathan, Francisco J. Gonzalez-Rico, Claudia M. Rejano-Gordillo, Ana Ordiales-Talavero, Jaime M. Merino, Pedro M. Fernandez-Salguero
Summary: This study reveals that the absence of aryl hydrocarbon receptor (AhR) in aging mice exacerbates cellular senescence and liver progenitor cell proliferation, leading to an increased risk of hepatocarcinoma. AhR plays a role in the regulation of senescence by repressing the expression of senescence-associated genes. Depletion of senescent cells or restoration of AhR levels can reverse the senescence phenotype. These findings highlight the importance of AhR in modulating age-induced senescence and its potential role in liver tumorigenesis.
Review
Cell Biology
Claudia Rejano-Gordillo, Ana Ordiales-Talavero, Ana Nacarino-Palma, Jaime M. Merino, Francisco J. Gonzalez-Rico, Pedro M. Fernandez-Salguero
Summary: The transcription factor aryl hydrocarbon receptor (AHR) is a key regulator involved in cell functions and tumor progression. It can act as either an oncogene or a tumor suppressor, depending on the specific organ, tissue and cell type. In addition to its role in cell adhesion and migration, AHR has potential as a therapeutic tool, diagnosis and prognosis marker.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Gastroenterology & Hepatology
Minyi Qian, Jun Liu, Danyang Zhao, Pengpeng Cai, Chuyue Pan, Wenxin Jia, Yingsheng Gao, Yufei Zhang, Nan Zhang, Yinan Zhang, Quan Zhang, Dalei Wu, Chengjie Shan, Meiling Zhang, Bernd Schnabl, Song Yang, Xu Shen, Lirui Wang
Summary: The intrinsic AHR in intestinal epithelial cells (IECs) plays a role in the development of alcohol-related liver disease (ALD) by modulating the intestinal microbiota and metabolite composition. AHR deficiency in IECs leads to the overgrowth of Helicobacter spp. in the gut, promoting their translocation to lymph nodes and liver and worsening liver injury. Isobutyric acid, an altered metabolite in Ahr(Delta IEC) mice, along with Helicobacter spp., exacerbates ethanol-induced liver injury. Activation of intestinal AHR with specific agonists protects mice from ALD development. Alcoholic patients have lower intestinal AHR expression and higher levels of Helicobacter spp.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Kristopher K. Abney, Jacques Galipeau
Summary: MSCs are promising investigational cellular therapeutics for tissue injury regeneration and immune-mediated diseases, with the transcription factor AhR playing a crucial role in inflammation, immunomodulation, and plasticity of these cells.
Review
Pharmacology & Pharmacy
Lucia Sladekova, Sridhar Mani, Zdenek Dvorak
Summary: The aryl hydrocarbon receptor (AhR) is a crucial member of the helix-loop-helix transcription factors family, playing a central role in host physiology and various pathophysiologies. Activation of AhR is ligand-driven and the pharmacology of activation is dependent on the type and quantity of ligand. Therefore, understanding AhR ligands is essential for further advancements in the field. This minireview clarifies misconceptions and explores the true nature of AhR activation by discussing selected chemical classes and their qualification as true receptor ligands.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Oncology
Sabah Akhtar, Shireen Hourani, Lubna Therachiyil, Abdullah Al-Dhfyan, Abdelali Agouni, Asad Zeidan, Shahab Uddin, Hesham M. Korashy
Summary: This article summarizes the characteristics and important roles of cancer stem cells (CSCs) and their connection with environmental toxin PAHs and cytosolic receptor AhR. The review also discusses the signaling pathways related to tumorigenesis and progression that are mediated by AhR, as well as the epigenetic regulations of CSCs by the AhR/CYP1A pathway.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jinyun Chen, Yujie Yang, Wade A. Russu, William K. Chan
Summary: The study reports that AHR undergoes chaperone-mediated autophagy in MDA-MB-468 triple-negative breast cancer cells, with specific characteristics and regulatory mechanisms involved in the degradation process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Debashree Chatterjee, Yuwei Zhang, Christ-Dominique Ngassaki-Yoka, Antoine Dutilleul, Soumia Khalfi, Olivier Hernalsteens, Tomas Raul Wiche Salinas, Jonathan Dias, Huicheng Chen, Yasmine Smail, Jean-Philippe Goulet, Brendan Bell, Jean-Pierre Routy, Carine Van Lint, Petronela Ancuta
Summary: The aryl hydrocarbon receptor (AhR) inhibits HIV-1 replication and outgrowth in TCR-activated CD4+ T cells. AhR blockade improves early/late reverse transcription, integration/translation, and viral outgrowth in CD4+ T cells of people living with HIV-1 receiving antiretroviral therapy. AhR blockade downregulates genes/pathways involved in HIV-1 interaction and gut-homing in CD4+ T cells of ART-treated PLWH, and HIC1 is identified as a direct AhR target.
Article
Oncology
Michael Kilian, Ron Sheinin, Chin Leng Tan, Mirco Friedrich, Christopher Kramer, Ayelet Kaminitz, Khwab Sanghvi, Katharina Lindner, Yu-Chan Chih, Frederik Cichon, Benjamin Richter, Stefanie Jung, Kristine Jahne, Miriam Ratliff, Robert M. Prins, Nima Etminan, Andreas von Deimling, Wolfgang Wick, Asaf Madi, Lukas Bunse, Michael Platten
Summary: Cancer immunotherapy relies on the fitness of cytotoxic and helper T cell responses. Dysfunctional cytotoxic T cell states in the tumor microenvironment (TME) are a main cause of resistance to immuno-therapy. Intratumoral myeloid cells, especially blood-borne myeloids (bbm), drive T cell dysfunction in the TME. This study demonstrates that major histocompatibility complex class II (MHCII)-restricted antigen presentation on bbm is crucial for controlling brain tumor growth.
Article
Oncology
Angelika Scherm, Franziska Maria Ippen, Peter Hau, Hansjoerg Baurecht, Wolfgang Wick, Jens Gempt, Helge Knuettel, Michael F. Leitzmann, Corinna Seliger
Summary: Glioblastoma is the most common malignant brain tumor in adults, and current standard treatment involves surgery followed by radiochemotherapy. This meta-analysis examined the efficacy of targeted therapies in newly diagnosed glioblastoma patients. The analysis showed that targeted agents did not significantly improve overall survival, but they did provide a benefit in progression-free survival, particularly in patients with an unmethylated MGMT promoter. Inhibition of VEGF with bevacizumab was the most effective in prolonging progression-free survival.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Oncology
Benjamin M. Ellingson, Patrick Y. Wen, Susan M. Chang, Martin van den Bent, Michael A. Vogelbaum, Gang Li, Shanpeng Li, Jiyoon Kim, Gilbert Youssef, Wolfgang Wick, Andrew B. Lassman, Mark R. Gilbert, John F. de Groot, Michael Weller, Evanthia Galanis, Timothy F. Cloughesy
Summary: This study reviewed past trials in recurrent glioblastoma and identified target objective response rates (ORRs) for different treatments. The study found that ORRs varied depending on the type of therapy, and ORR was significantly correlated with median overall survival (mOS) for chemotherapy, biologic, and immunotherapy trials. Based on this analysis, the study recommends a target ORR >25% and a sample size of >=40 patients for future studies in recurrent glioblastoma.
Article
Clinical Neurology
Matthias Wittayer, Claudia E. Weber, Maximilian Kittel, Michael Platten, Lucas Schirmer, Hayrettin Tumani, Achim Gass, Philipp Eisele
Summary: In patients with multiple sclerosis, iron rim lesions (IRLs) are associated with tissue damage, disease severity, and chronic active inflammation behind the blood-brain barrier. This study investigates CSF markers of intrathecal inflammation in patients with IRLs compared to patients without IRLs, as well as tissue damage in lesions and normal-appearing white matter (NAWM) near CSF spaces.
MULTIPLE SCLEROSIS JOURNAL
(2023)
Article
Clinical Neurology
Ann-Kathrin Nold, Matthias Wittayer, Claudia E. Weber, Michael Platten, Achim Gass, Philipp Eisele
Summary: This study aimed to investigate the short-term dynamics of brain atrophy development after initiation of disease-modifying therapy (DMT) in a real-world setting. The study found that the highest brain volume changes were observed in the first 12 months after initiation of natalizumab treatment.
JOURNAL OF NEUROIMAGING
(2023)
Article
Biochemistry & Molecular Biology
Niklas Grassl, Isabel Poschke, Katharina Lindner, Lukas Bunse, Iris Mildenberger, Tamara Boschert, Kristine Jahne, Edward W. Green, Ingrid Hulsmeyer, Simone Juenger, Tobias Kessler, Abigail K. Suwala, Philipp Eisele, Michael O. Breckwoldt, Peter Vajkoczy, Oliver M. Grauer, Ulrich Herrlinger, Joerg-Christian Tonn, Monika Denk, Felix Sahm, Martin Bendszus, Andreas von Deimling, Frank Winkler, Wolfgang Wick, Michael Platten, Katharina Sahm
Summary: The treatment of H3K27M-vac in patients with progressive H3K27M(+) diffuse midline glioma demonstrates its safety and immunogenicity, and may improve patients' survival.
Editorial Material
Biochemistry & Molecular Biology
Kirit Singh, Kelly M. Hotchkiss, Ian F. Parney, John De Groot, Solmaz Sahebjam, Nader Sanai, Michael Platten, Evanthia Galanis, Michael Lim, Patrick Y. Wen, Giuseppe Minniti, Howard Colman, Timothy F. Cloughesy, Minesh P. Mehta, Marjolein Geurts, Isabel Arrillaga-Romany, Annick Desjardins, Kirk Tanner, Susan Short, David Arons, Elizabeth Duke, Wolfgang Wick, Stephen J. Bagley, David M. Ashley, Priya Kumthekar, Roel Verhaak, Anthony J. Chalmers, Anoop P. Patel, Colin Watts, Peter E. Fecci, Tracy T. Batchelor, Michael Weller, Michael A. Vogelbaum, Matthias Preusser, Mitchel S. Berger, Mustafa Khasraw
Summary: A breakthrough in drug discovery for glioblastoma necessitates the consecutive collection of central nervous system tissue through window of opportunity trials.
Article
Oncology
Christoper Kraemer, Michael Kilian, Yu-Chan Chih, Alexandros Kourtesakis, Dirk C. Hoffmann, Tamara Boschert, Philipp Koopmann, Khwab Sanghvi, Alice De Roia, Stefanie Jung, Kristine Jaehne, Bryan Day, Lenny D. Shultz, Miriam Ratliff, Richard Harbottle, Edward W. Green, Rainer Will, Wolfgang Wick, Michael Platten, Lukas Bunse
Summary: This study identified an antigen that is overexpressed in human gliomas and can induce specific cytotoxic T cell responses through vaccination, indicating its potential therapeutic efficacy in treating glioblastoma.
Article
Biochemistry & Molecular Biology
Nikolaus von Knebel Doeberitz, Florian Kroh, Laila Koenig, Philip S. Boyd, Svenja Grass, Cora Bauspiess, Moritz Scherer, Andreas Unterberg, Martin Bendszus, Wolfgang Wick, Peter Bachert, Juergen Debus, Mark E. Ladd, Heinz-Peter Schlemmer, Steffen Goerke, Andreas Korzowski, Daniel Paech
Summary: The study aimed to evaluate the impact of blood products on the diagnostic interpretation of APT and ssMT imaging in the first follow-up MRI after radiotherapy. The results showed that the correction for blood products did not significantly affect the clinical performance of tumor imaging.
Article
Medicine, Research & Experimental
Hannah Kapell, Luca Fazio, Julia Dyckow, Sophia Schwarz, Andres Cruz-Herranz, Christina Mayer, Joaquin Campos, Elisa D'Este, Wiebke Moebius, Christian Cordano, Anne-Katrin Probstel, Marjan Gharagozloo, Amel Zulji, Venu Narayanan Naik, Anna Delank, Manuela Cerina, Thomas Muentefering, Celia Lerma-Martin, Jana K. Sonner, Jung Hyung Sin, Paul Disse, Nicole Rychlik, Khalida Sabeur, Manideep Chavali, Rajneesh Srivastava, Matthias Heidenreich, Kathryn C. Fitzgerald, Guiscard Seebohm, Christine Stadelmann, Bernhard Hemmer, Michael Platten, Thomas J. Jentsch, Maren Engelhardt, Thomas Budde, Klaus-Armin Nave, Peter A. Calabresi, Manuel A. Friese, Ari J. Green, Claudio Acuna, David H. Rowitch, Seven G. Meuth, Lucas Schirmer
Summary: Multiple sclerosis (MS) is a progressive inflammatory demyelinating disease of the CNS. Neuronal Kv7 and oligodendroglial Kir4.1 potassium channels play important roles in regulating neuronal excitability. Dysregulation of these channels in MS and experimental autoimmune encephalomyelitis (EAE) contributes to neuronal hyperexcitability. Pharmacological activation of nodal Kv7 channels provides neuroprotection against inflammatory demyelination.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Meeting Abstract
Rheumatology
Sven Wischnewski, Chiseko Ikenaga, Anna Kocharyan, Thomas Thaewel, Amel Zulji, Hans-Werner Rausch, Celia Lerma Martin, Dunja Mrdjen, David Brenner, Lukas Bunse, Chin Leng Tan, Leonie Thomas, Michael Kutza, Tim Trobisch, Corinna Preusse, Nicole Reed, Harald D. Von Pein, Angela Rosenbohm, Albert Ludolph, Ahmet Hoke, Michael Platten, Sean C. Bendall, Jochen H. Weishaupt, Clemens J. Sommer, Werner Stenzel, Thomas E. Lloyd, Lucas Schirmer
CLINICAL AND EXPERIMENTAL RHEUMATOLOGY
(2023)
Article
Neurosciences
A. P. Abu Hejleh, K. Huck, K. Jaehne, C. L. Tan, T. Lanz, L. Epping, J. K. Sonner, S. G. Meuth, A. Henneberg, C. A. Opitz, C. Herold-Mende, F. Sahm, M. Platten, K. Sahm
Summary: The vascular niche of malignant gliomas plays a critical role in shaping the immunosuppressive brain tumor microenvironment. The blood-brain-barrier formed by specialized endothelial cells and perivascular cells controls the migration and function of immune cells. The metabolism of tryptophan to kynurenine has been identified as an important pathway suppressing immune responses. However, the expression of endothelial IDO1 does not significantly affect brain tumor immunity.
INTERNATIONAL JOURNAL OF TRYPTOPHAN RESEARCH
(2023)
Article
Multidisciplinary Sciences
Nguyen T. Van, Karen Zhang, Rachel M. Wigmore, Anne I. Kennedy, Carolina R. Dasilva, Jialing Huang, Manju Ambelil, Jose H. Villagomez, Gerald J. O'Connor, Randy S. Longman, Miao Cao, Adam E. Snook, Michael Platten, Gerard Kasenty, Luis J. Sigal, George C. Prendergast, Sangwon V. Kim
Summary: Environmental factors, such as diet, can contribute to the development of colitis. This study demonstrates that dietary L-tryptophan promotes the development of GPR15+ Treg cells via the host IDO1/2 pathway and that tryptophan consumption in mice reduces the severity of colitis.
NATURE COMMUNICATIONS
(2023)
Meeting Abstract
Oncology
Lilli Sester, Anna Katharina Gambihler, Michael Kilian, Mirco Friedrich, Jan Frenking, Juliana de Castilhos, Lukas John, Elias Mai, Michael Platten, Carsten Mueller-Tidow, Niels Weinhold, Hartmut Goldschmidt, Christoph Stein-Thoeringer, Marc Raab
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Meeting Abstract
Oncology
Tim Wagner, Tim Wagner, Niklas Kehl, Simon Steiger, Michael Kilian, Tamara Boschert, Katharina Lindner, Bruno Schoenfelder, Karsten Rippe, Carsten-Mueller Tidow, Hartmut Goldschmidt, Marc Raab, Michael Platten, Stefan Eichmueller, Mirco Friedrich
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
