Review
Immunology
Patrick Grudzien, Henry Neufeld, Mbasogo Ebe Eyenga, Vadim Gaponenko
Summary: Chemokine G-protein coupled receptors are important drug targets for various diseases, but the development of chemokine receptor antagonists has been slow due to antagonist tolerance. The mechanisms underlying antagonist tolerance are poorly understood. This review provides a summary of the progress and challenges in therapeutic development of chemokine receptor antagonists, discusses the current knowledge of antagonist tolerance, and proposes new avenues for future investigation of this phenomenon. Additionally, it highlights the potential of modern methodologies in revealing novel mechanisms and advancing the development of tolerance-free antagonists.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Alan Le Mercier, Remy Bonnavion, Weijia Yu, Mohamad Wessam Alnouri, Sophie Ramas, Yang Zhang, Yannick Jaeger, Kenneth Anthony Roquid, Hyun-Woo Jeong, Kishor Kumar Sivaraj, Haaglim Cho, Xinyi Chen, Boris Strilic, Tjeerd Sijmonsma, Ralf Adams, Timm Schroeder, Michael A. Rieger, Stefan Offemanns
Summary: GPR182 is a new atypical chemokine receptor for CXCL10, CXCL12, and CXCL13, involved in regulating hematopoietic stem cell homeostasis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Biochemistry & Molecular Biology
C. Britton, M. C. Poznansky, P. Reeves
Summary: Historically, CXCR4 and CXCL12 are associated with the bone marrow niche and hematopoiesis, but CXCL12 has broad tissue expression. CXCR4 acts as a node impacting multiple cellular processes and disease, transitioning our perspective towards a polyfunctional signaling cascade.
Review
Pharmacology & Pharmacy
Katarzyna Mlyniec, Dominika Siodlak, Urszula Doboszewska, Gabriel Nowak
Summary: The relevance of oligomerization for the pharmacology of depression is supported by evidence mainly from in vitro studies and neuropsychopharmacological studies. It has been found that GPR39 may mediate the antidepressant action of monoaminergic antidepressants, indicating its potential as a target for novel antidepressant drugs. Further research on oligomerization is crucial for the development of new antidepressants.
PHARMACOLOGY & THERAPEUTICS
(2021)
Review
Pharmacology & Pharmacy
Sergi Ferre, Francisco Ciruela, Carmen W. Dessauer, Javier Gonzalez-Maeso, Terence E. Hebert, Ralf Jockers, Diomedes E. Logothetis, Leonardo Pardo
Summary: The study proposes the concept of GPCR-effect assemblies (GEMMAs), which are pre-assembled before receptor activation and allow more efficient interactions between specific signaling components. This offers an alternative model to the conventional collision coupling model and explains the differential properties of GPCRs in different cellular environments.
PHARMACOLOGY & THERAPEUTICS
(2022)
Review
Pharmacology & Pharmacy
Xiaoqing Guo, Qin Li, Shulan Pi, Yuanpeng Xia, Ling Mao
Summary: P2Y receptors are a critical group of G protein-coupled receptors that signal through dimers, playing diverse roles in physiology and pathology. Research has shown the significance of dimerization between P2Y receptors and other receptors in cardiovascular and cerebrovascular processes.
BIOCHEMICAL PHARMACOLOGY
(2021)
Review
Immunology
Yukari Okamoto, Sojin Shikano
Summary: Chemokine receptors, particularly GPR15, are important in maintaining immune homeostasis and inflammation development by directing leukocyte migration to tissues. In recent years, the discovery of GPR15 as a colon-homing receptor for T cells and its ligand, C10orf99, has brought attention to their roles in various inflammatory and immune disorders. Understanding the molecular mechanisms that regulate GPR15 expression and functions will help in the development of targeted therapeutics for GPR15-related diseases.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Tobias F. Fischer, Anne S. Czerniak, Tina Weiss, Clara T. Schoeder, Philipp Wolf, Oliver Seitz, Jens Meiler, Annette G. Beck-Sickinger
Summary: GPR1 plays a dual role in regulating chemerin activity, acting as a signaling receptor for arrestin-based signaling and as a scavenging receptor with broader ligand specificity.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Remy Bonnavion, Shangmin Liu, Haruya Kawase, Kenneth Anthony Roquid, Stefan Offermanns
Summary: A recent study discovered that GPR182, a novel chemokine receptor expressed in microvascular and lymphatic endothelial cells, plays a crucial role in immune regulation by binding to various chemokines and regulating their distribution. The study also found that GPR182 has a strong affinity for multiple chemokines, highlighting its importance in chemokine scavenging.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Olav Larsen, Sara Schuermans, Anna Walser, Stavroula Louka, Ida Aaberg Lillethorup, Jon Vabeno, Katrine Qvortrup, Paul Proost, Mette M. Rosenkilde
Summary: This study investigates the signaling capacity of peptides related to inflammatory chemokines. The peptides showed weak potency but retained their signaling on CCR1, while none of the peptides generated a signal on CCR5. However, a tetrapeptide derived from CCL3 acted as a positive modulator on CCR5.
Review
Biochemistry & Molecular Biology
Diego Guidolin, Cinzia Tortorella, Manuela Marcoli, Chiara Cervetto, Guido Maura, Luigi F. Agnati
Summary: The discovery of allosteric receptor-receptor interactions and receptor complexes in intercellular communication has expanded our understanding of the nervous system. Research on neuronal populations and receptor complexes has led to insights on synaptic efficiency tuning, with potential implications for neuroprotective therapeutic strategies. More research is still needed in this area to fully explore the implications of receptor-receptor interactions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Justine S. Paradis, Xiang Feng, Brigitte Murat, Robert E. Jefferson, Badr Sokrat, Martyna Szpakowska, Mireille Hogue, Nick D. Bergkamp, Franziska M. Heydenreich, Martine J. Smit, Andy Chevigne, Michel Bouvier, Patrick Barth
Summary: This article presents a computational approach for predicting receptor self-associations and designing receptor oligomers with various quaternary structures and signaling properties. Using this approach, the chemokine receptor CXCR4 dimers were successfully designed to have different conformations and abilities to activate distinct intracellular signaling proteins. The study also revealed the existence of a bias switch at the dimer interface of several G protein-coupled receptors, including CXCR4, mu-Opioid, and type-2 Vasopressin receptors, that selectively control the activation of G proteins vs beta-arrestin-mediated pathways.
NATURE COMMUNICATIONS
(2022)
Article
Endocrinology & Metabolism
Uchechukwu T. Agwuegbo, Emily Colley, Anthony P. Albert, Viktor Y. Butnev, George R. Bousfield, Kim C. Jonas
Summary: Recent studies have shown that the hypo-glycosylated FSH glycoform FSH21/18 is more bioactive than the fully-glycosylated FSH24. FSH21/18 predominates in women of reproductive prime while FSH24 is more common in peri-post-menopausal women. Differential FSH glycosylation modulates FSHR oligomerization, with high concentrations of FSH21/18 and FSH24 leading to dissociation of FSHR oligomers into monomers, and low concentrations promoting FSHR association into oligomers.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Kimia Kaffashi, Didier Dreau, Irina V. Nesmelova
Summary: Chemokines are signaling proteins that play a crucial role in cell-cell communication, migration, and trafficking. The oligomerization state of chemokines affects their biological activity, and heterooligomerization can significantly impact cellular responses. Recent studies on obligate heterodimers have provided valuable insights into the functional roles and molecular mechanisms of chemokine heterodimers. This review focuses on the latest progress in understanding the roles of chemokine heterodimers and their contribution to the functioning of the chemokine network.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Immunology
Seppe Cambier, Mieke Gouwy, Paul Proost
Summary: Chemokines play a crucial role in regulating leukocyte migration and activation in the immune system. CXCL8 is a potent chemokine that attracts neutrophils and is important in the response to infection and tissue injury. Its activity is dependent on interactions with specific chemokine receptors and glycosaminoglycans. Understanding the structure and regulation of CXCL8 is important for therapeutic development and managing inflammatory diseases and cancer.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Carmen Martinez, Yasmina Juarranz, Irene Gutierrez-Canas, Mar Carrion, Selene Perez-Garcia, Raul Villanueva-Romero, David Castro, Amalia Lamana, Mario Mellado, Isidoro Gonzalez-Alvaro, Rosa P. Gomariz
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Immunology
Blanca Soler Palacios, Concha Nieto, Pilar Fajardo, Arturo Gonzalez de la Aleja, Nuria Andres, Angeles Dominguez-Soto, Pilar Lucas, Ana Cuenda, Jose Miguel Rodriguez-Frade, Carlos Martinez-A, Ricardo Villares, Angel L. Corbi, Mario Mellado
JOURNAL OF IMMUNOLOGY
(2020)
Article
Immunology
Amalia Lamana, Ricardo Villares, Iria V. Seoane, Nuria Andres, Pilar Lucas, Paul Emery, Edward M. Vital, Ana Triguero-Martinez, Ana Marquez, Ana M. Ortiz, Robin Maxime, Carmen Martinez, Javier Martin, Rosa P. Gomariz, Frederique Ponchel, Isidoro Gonzalez-alvaro, Mario Mellado
FRONTIERS IN IMMUNOLOGY
(2020)
Editorial Material
Immunology
Jose Luis Rodriguez-Fernandez, Mario Mellado, Marcus Thelen, Philip M. Murphy
FRONTIERS IN IMMUNOLOGY
(2020)
Article
Immunology
Ana Marcos-Jimenez, Santiago Sanchez-Alonso, Ana Alcaraz-Serna, Laura Esparcia, Celia Lopez-Sanz, Miguel Sampedro-Nunez, Tamara Mateu-Albero, Ildefonso Sanchez-Cerrillo, Pedro Martinez-Fleta, Ligia Gabrie, Luciana del Campo Guerola, Jose Miguel Rodriguez-Frade, Jose M. Casasnovas, Hugh T. Reyburn, Mar Vales-Gomez, Margarita Lopez-Trascasa, Enrique Martin-Gayo, Maria Jose Calzada, Santos Castaneda, Hortensia de la Fuente, Isidoro Gonzalez-Alvaro, Francisco Sanchez-Madrid, Cecilia Munoz-Calleja, Arantzazu Alfranca
Summary: The immune response in peripheral blood of COVID-19 patients is associated with disease severity, with an imbalanced humoral response potentially being a characteristic of severe cases.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Article
Immunology
Yaiza Caceres-Martell, Daniel Fernandez-Soto, Carmen Campos-Silva, Eva M. Garcia-Cuesta, Jose M. Casasnovas, David Navas-Herrera, Alexandra Beneitez-Martinez, Pedro Martinez-Fleta, Arantzazu Alfranca, Francisco Sanchez-Madrid, Gabriela Escudero-Lopez, Carlos Vilches, Ricardo Jara-Acevedo, Hugh T. Reyburn, Jose M. Rodriguez-Frade, Mar Vales-Gomez
Summary: A new serological test has been developed to provide a more comprehensive picture of patient responses to multiple SARS-CoV-2 antigens, allowing for accurate discrimination between patients and healthy controls. Analyzing the response of multiple Ig isotypes to antigens in combination may help establish a correlation with disease severity. A more detailed description of immune responses to the SARS-CoV-2 virus among different patients could provide insight into the various clinical presentations of COVID-19.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Article
Cell Biology
Manuel Olazabal-Moran, Miriam Sanchez-Ortega, Laura Martinez-Munoz, Carmen Hernandez, Manuel S. Rodriguez, Mario Mellado, Ana C. Carrera
Summary: PI3-kinase and PTEN regulate the PIP3/AKT signaling pathway through the ubiquitin ligase cCBL, influencing cell survival, division, and migration. These findings reveal a novel mechanism for PI3-kinase/PTEN crosstalk and suggest that cCBL may be a potential target for modulating PTEN activity in cancer.
Article
Cell Biology
Alvaro Fernando Garcia-Jimenez, Yaiza Caceres-Martell, Daniel Fernandez-Soto, Pedro Martinez Fleta, Jose M. Casasnovas, Francisco Sanchez-Madrid, Jose Miguel Rodriguez Frade, Mar Vales-Gomez, Hugh T. Reyburn
Summary: Several unanswered questions remain about humoral and cellular immunity to SARS-CoV-2, including whether preexisting memory T or B cells in unexposed individuals can recognize and suppress COVID-19. Research has shown that while some unexposed individuals have cross-reactive T cell responses, these responses are weak in aspects like T-FH expansion, which may impact the generation of effective antibodies against SARS-CoV-2. Understanding these differences in cellular responses is crucial for advancing our knowledge of immunity to SARS-CoV-2.
JOURNAL OF LEUKOCYTE BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Elena R. Bovolenta, Eva M. Garcia-Cuesta, Lydia Horndler, Julia Ponomarenko, Wolfgang W. Schamel, Mario Mellado, Mario Castro, David Abia, Hisse M. van Santen
Summary: Signaling through T cell receptor (TCR) plays a critical role in the development, maintenance, and activation of T cells. This study reveals that the strength of pre-TCR-mediated signaling during T cell development determines the diversity of TCR beta repertoire for positive and negative selection.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Eva M. Garcia-Cuesta, Jose Miguel Rodriguez-Frade, Sofia R. Gardeta, Gianluca D'Agostino, Pablo Martinez, Blanca Soler Palacios, Graciela Cascio, Tobias Wolf, Nicolas Mateos, Rosa Ayala-Bueno, Cesar A. Santiago, Pilar Lucas, Lucia Llorente, Luis M. Allende, Luis Ignacio Gonzalez-Granado, Noa Martin-Cofreces, Pedro Roda-Navarro, Federica Sallusto, Francisco Sanchez-Madrid, Maria F. Garcia-Parajo, Laura Martinez-Munoz, Mario Mellado
Summary: This study reveals that the truncated mutant chemokine receptor CXCR4(R334X) associated with WHIM syndrome fails to nanoclusterize after CXCL12 stimulation, affecting cell spatial organization and mobility, and causing multiple phalloidin-positive protrusions in cells. The inappropriate activation of beta-arrestin1 by CXCR4(R334X) leads to inadequate actin cytoskeleton remodeling, disrupting the balance between activated and deactivated cofilin.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Immunology
Sofia R. Gardeta, Eva M. Garcia-Cuesta, Gianluca D'Agostino, Blanca Soler Palacios, Adriana Quijada-Freire, Pilar Lucas, Jorge Bernardino de la Serna, Carolina Gonzalez-Riano, Coral Barbas, Jose Miguel Rodriguez-Frade, Mario Mellado
Summary: The local lipid environment plays an important role in regulating CXCR4 organization and function, and modulating chemokine-triggered directed cell migration. Treatment of T cells with bacterial sphingomyelinase alters the lipid composition of the cell membrane, affecting membrane fluidity and CXCR4 nanoclustering and dynamics.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Blanca Soler Palacios, Ricardo Villares, Pilar Lucas, Jose Miguel Rodriguez-Frade, Ana Cayuela, Jonathan G. Piccirillo, Manuel Lombardia, David Delgado Gestoso, Miguel Fernandez-Garcia, Cristina Risco, Coral Barbas, Fernando Corrales, Carlos Oscar S. Sorzano, Nuria Martinez-Martin, Jose Javier Conesa, Francisco J. Iborra, Mario Mellado
Summary: This study found that growth hormone can alter the metabolism of inflammatory macrophages, increase mitochondrial volume and alter mitochondrial dynamics. It reduces glycolysis and lactate production, and increases the density of the inner mitochondrial membrane. The results suggest that targeting macrophage metabolism could be a new approach for intervening in inflammatory diseases.
FRONTIERS IN IMMUNOLOGY
(2023)