Article
Immunology
Paola Antonello, Diego U. Pizzagalli, Mathilde Foglierini, Serena Melgrati, Egle Radice, Sylvia Thelen, Marcus Thelen
Summary: Chemotaxis is an essential process in tumors metastasis, and in this study, ACKR3 was found to control the migration of lymphoma cells in response to CXCL12. The interaction between LTB4 and CXCL12 enhances the migration of lymphoma cells, providing a novel mechanism for cell-to-cell-induced migration.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Endocrinology & Metabolism
Vincent Duval, Paul Alayrac, Jean-Sebastien Silvestre, Angelique Levoye
Summary: Chemokines and their receptors play a crucial role in cardiovascular diseases. ACKR3, as an atypical chemokine receptor, has an exclusive role in CVD. Better understanding of ACKR3's precise functions may lead to the development of novel therapeutic strategies.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Multidisciplinary Sciences
Elena C. Sigmund, Aline Bauer, Barbara D. Jakobs, Hazal F. Tatliadim, Carlotta Tacconi, Marcus Thelen, Daniel F. Legler, Cornelia Halin
Summary: Atypical chemokine receptor 3 (ACKR3) acts as a scavenger for chemokines CXCL11 and CXCL12, as well as opioid peptides. It is also capable of binding the peptide hormone adrenomedullin (AM) and derivatives of proadrenomedullin N-terminal 20 peptide (PAMP). ACKR3-mediated AM scavenging by lymphatic endothelial cells (LECs) helps prevent overshooting AM-induced lymphangiogenesis and lymphatic hyperplasia. Furthermore, ACKR3-dependent scavenging of AM by human LECs does not occur at ligand concentrations sufficient to trigger AM-induced responses mediated by canonical AM receptors.
Article
Biochemistry & Molecular Biology
Kento Takaya, Toru Asou, Kazuo Kishi
Summary: The accumulation of senescent cells in aging tissues is associated with age-related diseases and functional decline. A study found that atypical chemokine receptor 3 (ACKR3) is selectively expressed on the surface of senescent human fibroblasts. This discovery allows for the selective elimination of senescent cells and could contribute to the development of novel senolysis approaches.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Elena C. Sigmund, Lilian Baur, Philipp Schineis, Jorge Arasa, Victor Collado-Diaz, Martina Vranova, Rolf A. K. Stahl, Marcus Thelen, Cornelia Halin
Summary: ACKR3 is a scavenging receptor implicated in lymphatic development, with deficiency leading to lymphatic hyperplasia and cardiac defects in mice. However, in adult mice, LEC-expressed ACKR3 does not contribute to postnatal lymphangiogenesis or lymphatic function.
Article
Pharmacology & Pharmacy
Brittany E. Hopkins, Ikuo Masuho, Dongjun Ren, Iredia D. Iyamu, Wei Lv, Neha Malik, Kirill A. Martemyanov, Gary E. Schiltz, Richard J. Miller
Summary: In this study, novel selective ligands for ACKR3 were discovered and the site of interactions between these small molecules and ACKR3 was defined. This work will help to better understand the unique signaling roles of ACKR3.
MOLECULAR PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Tom Van Loy, Steven De Jonghe, Karolien Castermans, Wouter Dheedene, Reinout Stoop, Lars Verschuren, Matthias Versele, Patrick Chaltin, Aernout Luttun, Dominique Schols
Summary: The ACKR3 agonist shows pharmacological activity in vitro and in vivo, with a modest anti-fibrotic effect in the liver fibrosis model. However, its inhibitory effect on lung fibrosis is lacking. More interventions in signaling pathways may be needed to achieve satisfactory clinical outcomes.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Martine J. Smit, Geraldine Schlecht-Louf, Maria Neves, Jelle van den Bor, Petronila Penela, Marco Siderius, Francoise Bachelerie, Federico Mayor
Summary: The elevated expression of chemokine receptors CXCR4 and ACKR3 and their ligand CXCL12 in tumors and the tumor microenvironment has led to complex research on their contribution to cancer pathogenesis. Discussions include their impact on signaling networks, crosstalk with RTKs and other TME factors, as well as the infiltration of immune cells supporting tumor progression. Targeting the CXCL12/CXCR4/ACKR3 axis along with RTKs and immune cells modulation shows promising therapeutic potential in multitargeted cancer therapies.
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 61, 2021
(2021)
Article
Cell Biology
Aurelien Zarca, Claudia Perez, Jelle van den Bor, Jan Paul Bebelman, Joyce Heuninck, Rianna J. F. de Jonker, Thierry Durroux, Henry F. Vischer, Marco Siderius, Martine J. Smit
Summary: The study revealed that ACKR3 recruits beta-arrestins and internalizes to the cell membrane upon CXCL12 stimulation, with GRK2 and 3 playing key roles in beta-arrestin recruitment and receptor internalization.
Article
Multidisciplinary Sciences
Anne-Katrin Rohlfing, Kyra Kolb, Manuel Sigle, Melanie Ziegler, Alexander Bild, Patrick Muenzer, Jessica Sudmann, Valerie Dicenta, Tobias Harm, Mailin-Christin Manke, Sascha Geue, Marcel Kremser, Madhumita Chatterjee, Chunguang Liang, Hendrik von Eysmondt, Thomas Dandekar, David Heinzmann, Manina Guenter, Saskia Von Ungern-Sternberg, Manuela Buettcher, Tatsiana Castor, Stine Mencl, Friederike Langhauser, Katharina Sies, Diyaa Ashour, Mustafa Caglar Beker, Michael Lammerhofer, Stella E. Autenrieth, Tilman E. Schaeffer, Stefan Laufer, Paulina Szklanna, Patricia Maguire, Matthias Heikenwalder, Karin Anne Lydia Mueller, Dirk M. Hermann, Ertugrul Kilic, Ralf Stumm, Gustavo Ramos, Christoph Kleinschnitz, Oliver Borst, Harald F. Langer, Dominik Rath, Meinrad Gawaz
Summary: Platelet activation and thrombus formation play a critical role in tissue injury during ischemia/reperfusion. The absence of ACKR3 on platelets enhances platelet activation and thrombosis, exacerbating tissue damage. Activation of platelet-ACKR3 can inhibit platelet activation and thrombus formation, attenuating tissue injury.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Yu-ting Lin, Hao-dong Chen, Qi-di Ai, Yan-tao Yang, Zhao Zhang, Shi-feng Chu, Nai-hong Chen
Summary: Chemokines, small molecular proteins, have a crucial role in immune and inflammatory responses after stroke. They are recognized as potential targets for stroke treatment, involved in neovascularization, neurogenesis, and neural network reconstruction. In this review, we summarized chemokine alterations during the post-stroke nerve repair phase to understand their pathological mechanisms and find effective therapeutic targets for stroke.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Shan Liu, Xiao-Bing Lan, Miao-Miao Tian, Chun-Hao Zhu, Lin Ma, Jia-Mei Yang, Juan Du, Ping Zheng, Jian-Qiang Yu, Ning Liu
Summary: Chronic pain poses a significant public health challenge, impacting patients' physical and psychological health as well as their quality of life. Current drug treatments for chronic pain often have limited efficacy and come with numerous side effects. The chemokine system, specifically the CCL2/CCR2 axis, plays a crucial role in the development and maintenance of chronic pain. Targeting this system through various approaches, such as siRNA, blocking antibodies, or small molecule antagonists, holds promise for managing chronic pain.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Oncology
Hina Mir, Neeraj Kapur, Dominique N. Gales, Praveen K. Sharma, Gabriela Oprea-Ilies, Anita T. Johnson, Rajesh Singh, Shailesh Singh
Summary: Breast cancer (BrCa) is the second leading cause of cancer-related deaths in American women, and its incidence is increasing. This study highlights the importance of the chemokine axis CXCR6/CXCL16 in promoting BrCa and suggests it as a potential therapeutic target for advanced-stage BrCa.
Review
Biochemistry & Molecular Biology
Pedro Bule, Sandra Isabel Aguiar, Frederico Aires-Da-Silva, Joana Nunes Ribeiro Dias
Summary: Chemokines play a crucial role in cancer development by influencing various processes such as angiogenesis, metastasis, and stemness. The chemokine network has emerged as a potential target for immunotherapy and may have therapeutic effects when used alone or in combination with other treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Albert Frank Magnusen, Reena Rani, Mary Ashley McKay, Shelby Loraine Hatton, Tsitsi Carol Nyamajenjere, Daniel Nii Aryee Magnusen, Joerg Koehl, Gregory Alex Grabowski, Manoj Kumar Pandey
Summary: Gaucher disease is a lysosomal storage disease caused by mutations in GBA1/Gba1. Deficiency of lysosomal acid beta-glucosidase enzyme leads to abnormal accumulation of glucosylceramide, resulting in altered function of immune cells and tissue damage. The study reveals the role of CXCR3 receptor and CXCL9 chemokine in increased recruitment of T cells in Gaucher disease, suggesting potential therapeutic targets for inflammation treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Francoise Bachelerie, Gerard J. Graham, Massimo Locati, Alberto Mantovani, Philip M. Murphy, Robert Nibbs, Antal Rot, Silvano Sozzani, Marcus Thelen
BRITISH JOURNAL OF PHARMACOLOGY
(2015)
Article
Immunology
Beth Lucas, Andrea J. White, Maria H. Ulvmar, Robert J. B. Nibbs, Katarzyna M. Sitnik, William W. Agace, William E. Jenkinson, Graham Anderson, Antal Rot
EUROPEAN JOURNAL OF IMMUNOLOGY
(2015)
Article
Biochemistry & Molecular Biology
Setareh Alampour-Rajabi, Omar El Bounkari, Antal Rot, Gerhard Mueller-Newen, Francoise Bachelerie, Meinrad Gawaz, Christian Weber, Andreas Schober, Juergen Bernhagen
Article
Gastroenterology & Hepatology
Daniel A. Patten, Garrick K. Wilson, Dalan Bailey, Robert K. Shaw, Sirpa Jalkanen, Marko Salmi, Antal Rot, Chris J. Weston, David H. Adams, Shishir Shetty
Article
Multidisciplinary Sciences
Olga G. Cordeiro, Melanie Chypre, Nathalie Brouard, Simon Rauber, Farouk Alloush, Monica Romera-Hernandez, Cecile Benezech, Zhi Li, Anita Eckly, Mark C. Coles, Antal Rot, Hideo Yagita, Catherine Leon, Burkhard Ludewig, Tom Cupedo, Francois Lanza, Christopher G. Mueller
Article
Oncology
S. T. Ward, K. K. Li, E. Hepburn, C. J. Weston, S. M. Curbishley, G. M. Reynolds, R. K. Hejmadi, R. Bicknell, B. Eksteen, T. Ismail, A. Rot, D. H. Adams
BRITISH JOURNAL OF CANCER
(2015)
Article
Immunology
Tamara Girbl, Tchern Lenn, Lorena Perez, Loic Rolas, Anna Barkaway, Aude Thiriot, Carlos del Fresno, Eleanor Lynam, Elin Hub, Marcus Thelen, Gerard Graham, Ronen Alon, David Sancho, Ulrich H. von Andrian, Mathieu-Benoit Voisin, Antal Rot, Sussan Nourshargh
Article
Cell Biology
Christoph Matti, Giulia D'Uonnolo, Marc Artinger, Serena Melgrati, Angela Salnikov, Sylvia Thelen, Vladimir Purvanov, Tobias D. Strobel, Lisa Spannagel, Marcus Thelen, Daniel F. Legler
JOURNAL OF LEUKOCYTE BIOLOGY
(2020)
Article
Cell Biology
Egle Radice, Rafet Ameti, Serena Melgrati, Mathilde Foglierini, Paola Antonello, Rolf A. K. Stahl, Sylvia Thelen, David Jarrossay, Marcus Thelen
Article
Biochemistry & Molecular Biology
Julia C. Gutjahr, Kyler S. Crawford, Davin R. Jensen, Prachi Naik, Francis C. Peterson, Guerric P. B. Samson, Daniel F. Legler, Johan Duchene, Christopher T. Veldkamp, Antal Rot, Brian F. Volkman
Summary: The pleiotropic chemokine CXCL12 is involved in various physiological and pathophysiological processes through engagement with different receptors. In addition to CXCR4 and ACKR3, CXCL12 was found to bind to the atypical receptor ACKR1 with high affinity, especially the dimeric form. This interaction between CXCL12 and ACKR1 may provide another level of regulation for the biological functions of CXCL12 and expand the role of ACKR1 in chemokine retention and presentation.
Article
Cell Biology
Kathrin Werth, Elin Hub, Julia Christine Gutjahr, Berislav Bosjnak, Xiang Zheng, Anja Bubke, Stefan Russo, Antal Rot, Reinhold Foerster
Summary: A study identifies a vascular compartment within the spleen, delineated by endothelial cells expressing ACKR4, which supports the homing of T cells into the spleen.
Article
Immunology
Johan Duchene, Igor Novitzky-Basso, Aude Thiriot, Maria Casanova-Acebes, Mariaelvy Bianchini, S. Leah Etheridge, Elin Hub, Katrin Nitz, Katharina Artinger, Kathrin Eller, Jorge Caamano, Thomas Rulicke, Paul Moss, Remco T. A. Megens, Ulrich H. von Andrian, Andres Hidalgo, Christian Weber, Antal Rot
Article
Biology
Aude Thiriot, Carolina Perdomo, Guiying Cheng, Igor Novitzky-Basso, Sara McArdle, Jamie K. Kishimoto, Olga Barreiro, Irina Mazo, Robinson Triboulet, Klaus Ley, Antal Rot, Ulrich H. von Andrian