Article
Oncology
Isis Benoit-Lizon, Elise Jacquin, Thaiz Rivera Vargas, Corentin Richard, Aurelie Roussey, Ludivine Dal Zuffo, Tiffany Martin, Andrea Melis, Daria Vinokurova, Sayyed Hamed Shahoei, Alvaro Baeza Garcia, Cassandre Pignol, Stephane Giorgiutti, Raphael Carapito, Romain Boidot, Frederique Vegran, Richard A. Flavell, Bernhard Ryffel, Eric R. Nelson, Pauline Soulas-Sprauel, Toby Lawrence, Lionel Apetoh
Summary: Activation of STING signaling enhances the differentiation and antitumor functions of T(H)1 and T(H)9 cells by increasing their production of IFN-gamma and interleukin-9, respectively. IRF3 and IFNARs are required for the enhancement of T(H)1 cell differentiation, while mTOR signaling is implicated in T(H)9 cell differentiation in response to STING activation. STING activation boosts the antitumor activity of T(H)1 and T(H)9 cells through their cytokine production, and enhances the efficacy of T(H)9 cells in adoptive transfer against melanoma.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Multidisciplinary Sciences
Laura A. Shaw, Tianda Z. Deng, Kyla D. Omilusik, Kennidy K. Takehara, Quynh P. Nguyen, Ananda W. Goldrath
Summary: CD4(+) T cells are important in vaccine development, but the existence of multiple helper subsets complicates the identification of memory precursor cells. Recent research has found that the expression of Id3 can identify a subset of CD4(+) T cells with memory potential, which exhibit significant re-expansion in response to secondary infection.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Immunology
Yunyun Zhu, Qiuyue Yu, Guannan Su, Na Shao, Jie Feng, Xiang Luo, Chunjiang Zhou, Peizeng Yang
Summary: This study investigated the mechanism of recombinant interferon-alpha 2a (IFN alpha 2a) in the treatment of Behcet's uveitis (BU) and found that IFN alpha 2a exerts its effects by modulating the function of dendritic cells (DCs) and CD4+ T cells.
CLINICAL IMMUNOLOGY
(2023)
Article
Biology
Ningbo Wu, Dongping Chen, Hongxiang Sun, Jianmei Tan, Yao Zhang, Tianyu Zhang, Yuheng Han, Hongzhi Liu, Xinxing Ouyang, Xiao-Dong Yang, Xiaoyin Niu, Jie Zhong, Zhengting Wang, Bing Su
Summary: The study reveals a novel regulatory role of MAP3K2 in intestinal T cell immunity via the IL-18-MAP3K2-JNK axis, providing a potential target for intervention in T cell-mediated colitis. MAP3K2-deficient T cells have reduced ability to induce colitis and affect Th1 cell differentiation in the intestine rather than Th17 cells.
SCIENCE CHINA-LIFE SCIENCES
(2021)
Article
Immunology
Peng Peng, Yue Lou, Junjun Wang, Shicheng Wang, Ping Liu, Lisa X. Xu
Summary: Recent studies have shown the effectiveness of highly activated, polyfunctional CD4(+) T cells in strengthening overall host antitumor immunity. Cryo-thermal therapy, which remodels the tumor microenvironment and induces antigen-specific CD4(+) T-cell responses, has been found to enhance antitumor immunity in vivo.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Arianna Draghi, Mario Presti, Agnete W. P. Jensen, Christopher A. Chamberlain, Benedetta Albieri, Anne-Christine K. Rasmussen, Mads H. Andersen, Michael D. Crowther, Inge Marie Svane, Marco Donia
Summary: Our study demonstrates that exploiting tumor-specific cytotoxic CD4(+) TILs could help overcome resistance to ICB mediated by IFN gamma-signaling loss in MHCIIconst(+) melanomas.
CLINICAL CANCER RESEARCH
(2023)
Review
Immunology
Weihang Luo, Jindong Hu, Weifang Xu, Jingcheng Dong
Summary: The immune response in the asthmatic respiratory tract is driven by CD4(+) T helper cells, especially Th2 cells. Asthma is a heterogeneous and progressive disease, with different stages of the disease course showing different immune responses. The complex immune networks in the inflammatory airway make it challenging to find a universal treatment for all asthmatics.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Gastroenterology & Hepatology
Ritian Lin, Caiyun Ma, Leilei Fang, Chunjin Xu, Cui Zhang, Xiaohan Wu, Wei Wu, Ruixin Zhu, Yingzi Cong, Zhanju Liu
Summary: TOB1 expression is decreased in IBD patients, and overexpression of TOB1 can suppress the differentiation of IBD CD4(+) T cells into Th1/Th17 cells. It inhibits Th1/Th17 cell differentiation through the Smad4/5-ID2 pathway.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Review
Immunology
Constance Renault, Nicolas Veyrenche, Franck Mennechet, Anne-Sophie Bedin, Jean-Pierre Routy, Philippe Van de Perre, Jacques Reynes, Edouard Tuaillon
Summary: Th17 cells play a crucial role in defending against pathogens at mucosal barriers, but they are also vulnerable to HIV-1 infection and depletion from gut mucosal sites. The imbalance caused by the loss of Th17 cells impairs cytokine production and leads to damage in the gut mucosal barrier, promoting HIV-1 disease progression. The expression of specific receptors by Th17 cells contributes to their susceptibility to HIV infection. Moreover, Th17 cells serve as long-lived viral reservoirs in HIV patients receiving antiretroviral therapy.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medicine, General & Internal
Tim K. Tsang, Kwok-Tai Lam, Yinping Liu, Vicky J. Fang, Xiaofeng Mu, Nancy H. L. Leung, J. S. Malik Peiris, Gabriel M. Leung, Benjamin J. Cowling, Wenwei Tu
Summary: The study found that T cell response, especially CD4 T cell response, is associated with homosubtypic and cross-strain protection against influenza infections. This protection is independent of the protection associated with HAI titer.
Article
Genetics & Heredity
Mahesh Pandit, Maheshwor Timilshina, Jae-Hoon Chang
Summary: Deficiency of LKB1 in T cells leads to preferential differentiation into Th1 and Th17 cells in the absence of inflammation, mediated by glycolysis. LKB1 regulates mTORC1 activity by phosphorylating PTEN, controlling effector T cell differentiation in a T cell-intrinsic manner.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2021)
Article
Immunology
Robert Krause, Christian M. Warren, Joshua D. Simmons, Peter F. Rebeiro, Fernanda Maruri, Farina Karim, Timothy R. Sterling, John R. Koethe, Al Leslie, Yuri F. van der Heijden
Summary: Patients with stable/increased HbA1c during TB treatment exhibited an increased pro-inflammatory state and elevated T cell activity. These changes were associated with unresolved dysglycemia and may indicate failure to fully resolve infection.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Daniel Chauss, Tilo Freiwald, Reuben McGregor, Bingyu Yan, Luopin Wang, Estefania Nova-Lamperti, Dhaneshwar Kumar, Zonghao Zhang, Heather Teague, Erin E. West, Kevin M. Vannella, Marcos J. Ramos-Benitez, Jack Bibby, Audrey Kelly, Amna Malik, Alexandra F. Freeman, Daniella M. Schwartz, Didier Portilla, Daniel S. Chertow, Susan John, Paul Lavender, Claudia Kemper, Giovanna Lombardi, Nehal N. Mehta, Nichola Cooper, Michail S. Lionakis, Arian Laurence, Majid Kazemian, Behdad Afzali
Summary: Research suggests that Vitamin D plays a crucial role in regulating the transcriptional response of T cells, leading to the transition from pro-inflammatory to suppressive cells. In patients with severe COVID-19, disruptions in Vitamin D signaling may be responsible for dysregulation of the immune system, resulting in increased inflammation.
Article
Pharmacology & Pharmacy
Abdolkarim Hosseini, Hadi Esmaeili Gouvarchin Ghaleh, Hossein Aghamollaei, Mahdi Fasihi Ramandi, Gholamhossein Alishiri, Alireza Shahriary, Kazem Hassanpour, Mahdi Tat, Gholamreza Farnoosh
Summary: Studies have shown that melatonin can be used as a medicinal adjuvant to treat COVID-19 by reducing and controlling inflammatory cytokines through regulating the expression of Th1 and Th2 regulatory genes.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Hye-Soo Park, Seunga Choi, Yong-Woo Back, Kang-In Lee, Han-Gyu Choi, Hwa-Jung Kim
Summary: The study found that PGE2 produced by RpfE-activated dendritic cells via the MAPK and cyclooxygenase 2 signaling pathways induces Th1 and Th17 cell responses mainly via the EP4 receptor, contributing to defense against Mycobacterium tuberculosis infection. Moreover, adding optimal amount of PGE2 to IL-2-IL-6-IL-23p19-IL-1 beta is essential for promoting differentiation into Th1/Th17 cells with strong bactericidal activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Cristian Donas, Jocelyn Neira, Francisco Osorio-Barrios, Macarena Carrasco, Dominique Fernandez, Carolina Prado, Alejandra Loyola, Rodrigo Pacheco, Mario Rosemblatt
Summary: Dendritic cells play a crucial role in inflammatory disorders, particularly in inflammatory bowel diseases (IBD). Using the inhibitor GSK-J4 can alleviate inflammatory colitis by reducing the inflammatory potential of dendritic cells and enhancing the activity of regulatory T cells.
SCIENTIFIC REPORTS
(2021)
Article
Gastroenterology & Hepatology
Francisco Osorio-Barrios, Gemma Navarro, Javier Campos, Valentina Ugalde, Carolina Prado, Lu Raich, Francisco Contreras, Ernesto Lopez, Alexandra Espinoza, Alvaro Lladser, Rafael Franco, Rodrigo Pacheco
Summary: This study reveals that the heteromeric complex formed by CCR9 and the dopamine receptor D-5 (DRD5) is the key receptor providing colonic tropism to effector CD4(+) T cells in gut inflammation, as opposed to CCR9 alone. The CCR9:DRD5 heteroreceptor is upregulated in the intestinal mucosa of IBD patients. Signaling assays demonstrate that these complexes behave differently than individual receptors.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Hugo Gonzalez, Wenbin Mei, Isabella Robles, Catharina Hagerling, Breanna M. Allen, Trine Line Hauge Okholm, Ankitha Nanjaraj, Tamara Verbeek, Sandhya Kalavacherla, Merel van Gogh, Stephen Georgiou, Mariza Daras, Joanna J. Phillips, Matthew H. Spitzer, Jeroen P. Roose, Zena Werb
Summary: This study provides an integrative analysis of brain metastasis using single-cell transcriptomics, mass cytometry, and mouse models. It identifies two functional archetypes of brain metastasis and provides a foundation for understanding the molecular basis of this disease.
Article
Immunology
Carolina Prado, Francisco Osorio-Barrios, Paulina Falcon, Alexandra Espinoza, Juan Jose Saez, Maria Isabel Yuseff, Rodrigo Pacheco
Summary: Recent evidence has shown dopamine as a major regulator of inflammation, with dopaminergic regulation of immune cells playing an important role in inflammatory disorders. The study addressed the role of dopamine receptor D3 in B cells in animal models of multiple sclerosis (MS) and found that selective Drd3 deficiency in B cells abolished disease development in one model while exacerbating disease severity in another, demonstrating a dual role of DRD3 in CNS-autoimmunity.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Neurosciences
Rodrigo Moraga-Amaro, Raul Diaz-Galarce, Juan P. Donoso-Ramos, Valentina Ugalde, Sergio Linsambarth, Janine Doorduin, Erik FJ. de Vries, Estibaliz Ampuero, Francisca Pena, Rodrigo Pacheco, Ursula Wyneken, Jimmy Stehberg
Summary: This study evaluated the effects of prenatal fluoxetine exposure on memory and emotional behavior of rat offspring. Results showed that male rats exposed to fluoxetine during gestation displayed memory impairments and increased anxiety- and depressive-like symptoms in adulthood.
Article
Immunology
Paulina Garcia-Gonzalez, Dominique Fernandez, Diane Gutierrez, Mauro Parra-Cordero, Fabiola Osorio
Summary: This study demonstrates that human cDC1s constitutively activate the IRE1 enzyme to maintain cellular homeostasis at steady state, and the activation of the IRE1/XBP1s axis is a conserved feature of cDC1s across species, suggesting that the UPR sensor may also play a relevant role in the biology of the human lineage.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Article
Oncology
Ran You, Jordan Artichoker, Arja Ray, Hugo Gonzalez Velozo, Dan A. Rock, Kip P. Conner, Matthew F. Krummel
Summary: This study characterized the exposure and pharmacodynamic response of an anti-muCD3/anti-huEGFRvIII mouse surrogate BiTE molecule in EGFR variant III-positive breast tumors using intravital imaging. The results revealed heterogeneous temporal and spatial dynamics of BiTE molecule extravasation into solid tumors, indicating physical barriers to its function. High and homogeneous EGFRvIII expression on cancer cells was found to be necessary for efficient tumor clearance by the BiTE molecule. Additionally, the optimal tumor killing required resident tumor-infiltrating lymphocytes (TIL) at high BiTE molecule dosage, while inclusion of peripheral T-cell recruitment was synergistic at moderate to low dosages. Deletion of stimulating conventional type I dendritic cells (cDC1) diminished T-cell activation and tumor clearance induced by the BiTE molecule, suggesting the modulation of in situ antigen-presenting cell (APC) engagements on its efficacy.
CANCER IMMUNOLOGY RESEARCH
(2022)
Article
Medicine, General & Internal
Leonardo Vargas, Nicolas Valdivieso, Fabian Tempio, Valeska Simon, Daniela Sauma, Lucia Valenzuela, Caroll Beltran, Loriana Castillo-Delgado, Ximena Contreras-Benavides, Monica L. Acevedo, Johanna Acevedo, Rafael I. Gonzalez, Fernando Valiente-Echeverria, Ricardo Soto-Rifo, Mario Rosemblatt, Mercedes Lopez, Fabiola Osorio, Maria Rosa Bono
Summary: This study compares the immunogenicity and time course of the humoral response elicited by the CoronaVac vaccine with homologous and heterologous boosters. The results show that CoronaVac induces lower levels of antibodies compared to the BNT162b2 vaccine, but the response can be greatly enhanced with a heterologous booster scheme. Additionally, both homologous and heterologous boosters induce a durable antibody response that remains effective after 3 months.
Article
Immunology
Franca Marino, Monica Pinoli, Emanuela Rasini, Stefano Martini, Alessandra Luini, Laura Pulze, Daniela Dalla Gasperina, Paolo Grossi, Massimiliano Legnaro, Marco Ferrari, Terenzio Congiu, Rodrigo Pacheco, Francisco Osorio-Barrios, Magda de Eguileor, Marco Cosentino
Summary: Dopamine affects human polymorphonuclear leukocytes by acting on dopamine receptors, resulting in inhibition of cell migration and reactive oxygen species production. This effect varies between healthy individuals and patients with bacterial infections.
Article
Cell Biology
Mauricio Campos-Mora, Javiera De Solminihac, Carolina Rojas, Cristina Padilla, Monica Kurte, Rodrigo Pacheco, Thilo Kaehne, Ursula Wyneken, Karina Pino-Lagos
Summary: This study demonstrates that Treg cells secrete sEV containing Nrp1, which play a crucial role in regulating the phenotype and proliferation of effector CD4+ T cells, as well as promoting skin transplantation tolerance.
JOURNAL OF EXTRACELLULAR VESICLES
(2022)
Article
Cell Biology
Ornella Chovar-Vera, Ernesto Lopez, Felipe Galvez-Cancino, Carolina Prado, Dafne Franz, Diego A. Figueroa, Alexandra Espinoza, Claudio Figueroa, Alvaro Lladser, Rodrigo Pacheco
Summary: Dopamine, as an important regulator of immunity, exerts both anti-inflammatory and immunostimulatory effects depending on the activation of different types of dopamine receptors. This study demonstrates the crucial role of dopamine receptor D3 (DRD3) in CD8(+) T-cell function and its impact on anti-tumour immune response. The stimulation of DRD3 promotes IL-2 production and CD25 expression, leading to enhanced expansion and effector differentiation of CD8(+) T-cells. These findings contribute to a better understanding of dopaminergic regulation of cellular immunity and provide insights for the improvement of melanoma therapy.
Article
Immunology
Carolina Prado, Alexandra Espinoza, J. Eduardo Martinez-Hernandez, Joseph Petrosino, Erick Riquelme, Alberto J. M. Martin, Rodrigo Pacheco
Summary: Gut microbiota plays a critical role in immune homeostasis and dysbiosis is associated with autoimmune disorders. In this study, a reduction of bacteria belonging to Clostridia clusters IV and XIVa, major producers of SCFAs, was found in CNS autoimmunity. The study also revealed the role of SCFA-mediated effects on mucosal T-cells in the development of CNS autoimmunity.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Cell Biology
Francisca Gutierrez-Ballesteros, Jonathan Morales-Reyes, Dominique Fernandez, Antonia Geisse, Amada Arcaya, Felipe Flores-Santibanez, Maria Rosa Bono, Fabiola Osorio
Summary: DCs are crucial for adaptive immunity and the unfolded protein response sensors, such as IRE1/XBP1s axis, play a role in their development and survival. The role of ATF6a in DC biology has not been clearly elucidated, but it contributes to the production of IL-12 and IL-6 in activated DCs, suggesting its involvement in regulating immune features.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Meeting Abstract
Immunology
Fabiola Osorio, Felipe Flores, Dominique Fernandez
JOURNAL OF IMMUNOLOGY
(2022)