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REVIEW
Helio Salgado Cesar, Fernanda Brognara, Aline Barbosa Ribeiro, Renata Maria Lataro, Jaci Airton Castania, Luis Ulloa, Alexandre Kanashiro
Bioelectronic medicine is a novel field in modern medicine based on specific neuronal stimulation to control organ function and cardiovascular and immune homeostasis. However, most studies addressing neuromodulation of the immune system have been conducted on anesthetized animals, which can affect the nervous system and neuromodulation. Here we review recent studies involving conscious experimental rodents (rats and mice) to better understand the functional organization of neural control of immune homeostasis...
May 5, 2023: Neuroimmunomodulation
#22
REVIEW
Hélio Amante Miot, Paulo Ricardo Criado, Caio César Silva de Castro, Mayra Ianhez, Carolina Talhari, Paulo Müller Ramos
The JAK-STAT signaling pathway mediates important cellular processes such as immune response, carcinogenesis, cell differentiation, division and death. Therefore, drugs that interfere with different JAK-STAT signaling patterns have potential indications for various medical conditions. The main dermatological targets of JAK-STAT pathway inhibitors are inflammatory or autoimmune diseases such as psoriasis, vitiligo, atopic dermatitis and alopecia areata; however, several dermatoses are under investigation to expand this list of indications...
2023: Anais Brasileiros de Dermatologia
#23
JOURNAL ARTICLE
Fernando Alvarez, Roman Istomine, Alonso Da Silva Lira Filho, Tho-Alfakar Al-Aubodah, Daniel Huang, Rakan Okde, Martin Olivier, Jörg H Fritz, Ciriaco A Piccirillo
Survival and pulmonary recuperation following Influenza A (IAV) infection requires a well-orchestrated balance between pro-inflammatory and regulatory cells of the immune response. IL-18, a member of the IL-1 family of alarmins, is abundantly released in the lungs during IAV infections where it promotes anti-viral TH 1 responses. However, there is cumulating evidence that TREG cells can also recognize IL-18, although the mechanisms involved remain ill-defined. Through genetic disruption of the IL-18 receptor, we demonstrate that IL-18 not only promotes pulmonary TH 1 responses, but also influences TREG function in the infected lungs...
May 12, 2023: Mucosal Immunology
#24
JOURNAL ARTICLE
Cameron W Paterson, Melissa B Gutierrez, Craig M Coopersmith, Mandy L Ford
INTRODUCTION: Chronic alcohol use poses significant negative consequences to public health and, among its many biologic effects, is associated with significant T cell dysregulation within the adaptive immune system that has yet to be fully characterized. Novel, automated strategies for high dimensional flow cytometric analysis of the immune system are rapidly improving researchers' ability to detect and characterize rare cell types. METHODS: Using a murine model of chronic alcohol ingestion in conjunction with viSNE and CITRUS analysis tools, we performed a machine-driven, exploratory analysis comparing rare splenic subpopulations within the conventional CD4+ , regulatory CD4+ and CD8+ T cell compartments between alcohol- and water-fed animals...
2023: Frontiers in Immunology
#25
JOURNAL ARTICLE
Geovana C Ferreira, Thainara V C Sanches, Marina L Mechler-Dreibi, Henrique M S Almeida, Gabriel Y Storino, Karina Sonalio, Fernando A M Petri, Tereza S Martins, Luís Carlos Cides da Silva, Hélio J Montassier, Osvaldo A Sant'Anna, Márcia C A Fantini, Luís Guilherme de Oliveira
Mycoplasma hyopneumoniae, the main etiological agent of Porcine Enzootic Pneumonia, is widely spread in swine production worldwide. Its prevention is of great interest for the productive system, since its colonization in the lung tissue leads to intense production losses. This study aimed to compare the M. hyopneumoniae shedding and acute-phase response in 30 pigs submitted to different vaccination protocols: an experimental oral vaccine using a nanostructured mesoporous silica (SBA-15) as adjuvant (n = 10); an intramuscular commercially available vaccine at 24 days of age (n = 10); and a control group (n = 10) following experimental challenge with M...
March 26, 2023: Research in Veterinary Science
#26
JOURNAL ARTICLE
Túllio T Deusdará, Mellanie K C Félix, Helio de S Brito, Edson W S Cangussu, Wellington de S Moura, Benedito Albuquerque, Marcos G Silva, Gil R Dos Santos, Paula B de Morais, Elizangela F da Silva, Yury O Chaves, Luis Andre M Mariúba, Paulo A Nogueira, Spartaco Astolfi-Filho, Enedina N Assunção, Sabrina Epiphanio, Claudio R F Marinho, Igor V Brandi, Kelvinson F Viana, Eugenio E Oliveira, Alex Sander R Cangussu
Acinetobacter baumannii is a Gram-negative, immobile, aerobic nosocomial opportunistic coccobacillus that causes pneumonia, septicemia, and urinary tract infections in immunosuppressed patients. There are no commercially available alternative antimicrobials, and multi-drug resistance is an urgent concern that requires emergency measures and new therapeutic strategies. This study evaluated a multi-drug-resistant A. baumannii whole-cell vaccine, inactivated and adsorbed on an aluminum hydroxide-chitosan (mAhC) matrix, in an A...
March 16, 2023: Vaccines
#27
RANDOMIZED CONTROLLED TRIAL
Riccardo Calvani, Jacopo Gervasoni, Anna Picca, Francesca Ciciarello, Vincenzo Galluzzo, Hélio José Coelho-Júnior, Clara Di Mario, Elisa Gremese, Sara Lomuscio, Anna Maria Paglionico, Lavinia Santucci, Barbara Tolusso, Andrea Urbani, Federico Marini, Emanuele Marzetti, Francesco Landi, Matteo Tosato
Altered l-arginine metabolism has been described in patients with COVID-19 and has been associated with immune and vascular dysfunction. In the present investigation, we determined the serum concentrations of l-arginine, citrulline, ornithine, monomethyl-l-arginine (MMA), and symmetric and asymmetric dimethylarginine (SDMA, ADMA) in adults with long COVID at baseline and after 28-days of l-arginine plus vitamin C or placebo supplementation enrolled in a randomized clinical trial, compared with a group of adults without previous history of SARS-CoV-2-infection...
March 7, 2023: International Journal of Molecular Sciences
#28
JOURNAL ARTICLE
Stephanie R Peterson, Soham Ali, Rachel L Shrode, Ashutosh K Mangalam
Multiple sclerosis (MS) is an autoimmune demyelinating disease of the CNS that is linked with both genetic and environmental factors. A Western-style diet rich in fat and simple sugars is hypothesized as a potential factor contributing to the increased incidence of inflammatory autoimmune diseases, such as MS, in developed countries. Although the adverse effects of a high-fat diet in MS have been studied extensively, the effect of a fructose-rich diet (FRD) on MS etiology is unknown. We hypothesized that an FRD will alter the gut microbiome, influence immune populations, and negatively impact disease in experimental autoimmune encephalomyelitis (EAE), an animal model of MS...
March 1, 2023: ImmunoHorizons
#29
JOURNAL ARTICLE
Elisa Cruz-Morales, Andrew P Hart, Georgia M Fossett, Terri M Laufer
Foxp3+ regulatory T cells (Tregs) are essential for intestinal homeostasis. Tregs in the small intestine include Helios+ thymus-derived Tregs (tTregs) and RORγt+ Tregs that differentiate in the periphery after antigenic stimulation (pTregs). TCR and costimulatory signals sustain Tregs with effector phenotypes, including those in the intestine, but it is unknown if tTregs and pTregs have similar requirements for these pathways. We previously used mice lacking peripheral expression of MHCII to demonstrate that the small intestine sustains tTregs independently of peripheral antigen...
March 18, 2023: Mucosal Immunology
#30
JOURNAL ARTICLE
Eric S Wang, Nathanael S Gray
In this issue of Cell Chemical Biology, Bonazzi et al. demonstrate that pharmacologically degrading the transcription factor Helios (IKZF2) results in destabilization of regulatory T cells, which normally restrain anti-tumor immunity. These results highlight how molecular glue degraders can selectively target previously undruggable proteins with potential applications in the clinic.
March 16, 2023: Cell Chemical Biology
#31
JOURNAL ARTICLE
Sudhir Kumar Chauhan, Raquel Bartolomé Casado, Ole J B Landsverk, Hanna Johannessen, Danh Phung, Hogne Røed Nilsen, Frank Sætre, Jørgen Jahnsen, Rune Horneland, Sheraz Yaqub, Einar Martin Aandahl, Knut E A Lundin, Espen S Bækkevold, Frode L Jahnsen
BACKGROUND: Regulatory CD4 T cells (Tregs) in the mice gut are mainly specific for intestinal antigens and play an important role in the suppression of immune responses against harmless dietary antigens and members of the microbiota. However, information about the phenotype and function of Tregs in the human gut is limited. OBJECTIVE: Here, we performed a detailed characterization of Foxp3+ CD4 Tregs in human normal small intestine (SI) as well as from transplanted duodenum and celiac disease lesions...
March 7, 2023: Journal of Allergy and Clinical Immunology
#32
JOURNAL ARTICLE
Simone Bonazzi, Eva d'Hennezel, Rohan E J Beckwith, Lei Xu, Aleem Fazal, Anna Magracheva, Radha Ramesh, Artiom Cernijenko, Brandon Antonakos, Hyo-Eun C Bhang, Roxana García Caro, Jennifer S Cobb, Elizabeth Ornelas, Xiaolei Ma, Charles A Wartchow, Matthew C Clifton, Ry R Forseth, Bethany Hughes Fortnam, Hongbo Lu, Alfredo Csibi, Jennifer Tullai, Seth Carbonneau, Noel M Thomsen, Jay Larrow, Barbara Chie-Leon, Dominik Hainzl, Yi Gu, Darlene Lu, Matthew J Meyer, Dylan Alexander, Jacqueline Kinyamu-Akunda, Catherine A Sabatos-Peyton, Natalie A Dales, Frédéric J Zécri, Rishi K Jain, Janine Shulok, Y Karen Wang, Karin Briner, Jeffery A Porter, John A Tallarico, Jeffrey A Engelman, Glenn Dranoff, James E Bradner, Michael Visser, Jonathan M Solomon
Malignant tumors can evade destruction by the immune system by attracting immune-suppressive regulatory T cells (Treg) cells. The IKZF2 (Helios) transcription factor plays a crucial role in maintaining function and stability of Treg cells, and IKZF2 deficiency reduces tumor growth in mice. Here we report the discovery of NVP-DKY709, a selective molecular glue degrader of IKZF2 that spares IKZF1/3. We describe the recruitment-guided medicinal chemistry campaign leading to NVP-DKY709 that redirected the degradation selectivity of cereblon (CRBN) binders from IKZF1 toward IKZF2...
February 25, 2023: Cell Chemical Biology
#33
REVIEW
Víctor Jimenez-Coll, Santiago Llorente, Francisco Boix, Rafael Alfaro, José Antonio Galián, Helios Martinez-Banaclocha, Carmen Botella, María R Moya-Quiles, Manuel Muro-Pérez, Alfredo Minguela, Isabel Legaz, Manuel Muro
The process and evolution of an organ transplant procedure has evolved in terms of the prevention of immunological rejection with the improvement in the determination of immune response genes. These techniques include considering more important genes, more polymorphism detection, more refinement of the response motifs, as well as the analysis of epitopes and eplets, its capacity to fix complement, the PIRCHE algorithm and post-transplant monitoring with promising new biomarkers that surpass the classic serum markers such as creatine and other similar parameters of renal function...
February 15, 2023: International Journal of Molecular Sciences
#34
JOURNAL ARTICLE
Hélios Bertin, Sophie Peries, Jérôme Amiaud, Nathalie Van Acker, Bastien Perrot, Corinne Bouvier, Sébastien Aubert, Béatrice Marie, Frédérique Larousserie, Gonzague De Pinieux, Vincent Crenn, Françoise Rédini, Anne Gomez-Brouchet
Background-The purpose of this study was to investigate the bone resorption, as well as the vascular and immune microenvironment, of jaw osteosarcomas (JO) and to correlate these features with patient clinical outcomes. Methods-We studied 50 JO biopsy samples by immunohistochemical analysis of tissue microarrays (TMAs). We investigated the bone remodeling markers RANK/RANKL/OPG, the endothelial glycoprotein CD146, and biomarkers of the immune environment (CD163 and CD68 of macrophages, CD4+ and CD8+ of tumor-infiltrating lymphocytes (TILs), and an immune checkpoint PD-1/PD-L1)...
February 4, 2023: Cancers
#35
JOURNAL ARTICLE
Guilherme M J Costa, Samyra M S N Lacerda, André F A Figueiredo, Natália T Wnuk, Marcos R G Brener, Lídia M Andrade, Gabriel H Campolina-Silva, Andrea Kauffmann-Zeh, Lucila G G Pacifico, Alice F Versiani, Maísa M Antunes, Fernanda R Souza, Geovanni D Cassali, André L Caldeira-Brant, Hélio Chiarini-Garcia, Fernanda G de Souza, Vivian V Costa, Flavio G da Fonseca, Maurício L Nogueira, Guilherme R F Campos, Lucas M Kangussu, Estefânia M N Martins, Loudiana M Antonio, Cintia Bittar, Paula Rahal, Renato S Aguiar, Bárbara P Mendes, Marcela S Procópio, Thiago P Furtado, Yuri L Guimaraes, Gustavo B Menezes, Ana Martinez-Marchal, Kyle E Orwig, Miguel Brieño-Enríquez, Marcelo H Furtado
BACKGROUND: Cellular entry of SARS-CoV-2 has been shown to rely on angiotensin-converting enzyme 2 (ACE2) receptors, whose expression in the testis is among the highest in the body. Additionally, the risk of mortality seems higher among male COVID-19 patients, and though much has been published since the first cases of COVID-19, there remain unanswered questions regarding SARS-CoV-2 impact on testes and potential consequences for reproductive health. We investigated testicular alterations in non-vaccinated deceased COVID-19-patients, the precise location of the virus, its replicative activity, and the immune, vascular, and molecular fluctuations involved in the pathogenesis...
February 16, 2023: BMC Biology
#36
JOURNAL ARTICLE
Mona Tarighi, Mehdi Shahbazi, Payam Saadat, Abdolreza Daraei, Ali Alizadeh Khatir, Kimiya Rahimifard, Mousa Mohammadnia-Afrouzi
BACKGROUND: Multiple sclerosis (MS) is an aggressive disease characterized by central nervous system (CNS) inflammatory and demyelinating lesions. Tolerance failure is implicated in the development of several autoimmune disorders, including MS. Due to their involvement in maintaining environmental tolerance, regulatory T cells (Tregs) are regarded as efficient immune cells. We examined the frequency of Tregs in this study using CD4/CD25/forkhead box protein P3 (FOXP3)/Helios markers. METHODS: Fifty participants, including 25 patients with secondary progressive MS (SPMS) and 25 healthy controls (HCs), were enrolled in this study, and their demographic characteristics were recorded...
February 2, 2023: International Immunopharmacology
#37
Casey R Ager, Mingxuan Zhang, Matthew Chaimowitz, Shruti Bansal, Aleksandar Obradovic, Meri Rogava, Johannes C Melms, Patrick McCann, Catherine Spina, Charles G Drake, Matthew C Dallos, Benjamin Izar
Current methods for biomarker discovery and target identification in immuno-oncology rely on static snapshots of tumor immunity. To thoroughly characterize the temporal nature of antitumor immune responses, we developed a 34-parameter spectral flow cytometry panel and performed high-throughput analyses in critical contexts. We leveraged two distinct preclinical models that recapitulate cancer immunoediting (NPK-C1) and immune checkpoint blockade (ICB) response (MC38), respectively, and profiled multiple relevant tissues at and around key inflection points of immune surveillance and escape and/or ICB response...
January 2, 2023: bioRxiv
#38
EDITORIAL
Orli Carvalho da Silva Filho, Helio Rocha Neto
The COVID-19 pandemic has resulted in widespread reflection in medical communities about the role of professional stakeholders in public health interventions. Health professionals, including mental health clinicians, should question how, when, and why they should intervene to address the obstacles and objections to these interventions.
January 23, 2023: Journal of the American Academy of Child and Adolescent Psychiatry
#39
JOURNAL ARTICLE
Haobing Cai, Yu Liu, Xiaohua Dong, Fei Jiang, Hongliang Li, Song Ouyang, Weifan Yin, Ting He, Qiuming Zeng, Huan Yang
INTRODUCTION: Neuromyelitis optica spectrum disorder (NMOSD) is a group of antibody-mediated inflammatory demyelinating central nervous system diseases. T lymphocytes participate in NMOSD pathogenesis, with regulatory T cells (Treg) being the core in maintaining immune homeostasis. Studies have revealed that different Treg subsets play different roles in autoimmune diseases. The distribution of LAP+ or GARP+ Treg subsets in NMOSD may help us deeply understand their immune mechanism. METHODS: This study reviewed 22 NMOSD patients and 20 normal controls...
January 23, 2023: Neurological Sciences
#40
JOURNAL ARTICLE
Lu Cao, Xiaoqian Ma, Juan Zhang, Min Yang, Zhenhu He, Cejun Yang, Sang Li, Pengfei Rong, Wei Wang
Clinically, xenotransplantation often leads to T-cell-mediated graft rejection. Immunosuppressive agents including polyclonal regulatory T cells (poly-Tregs) promote global immunosuppression, resulting in serious infections and malignancies in patients. Xenoantigen-expanded Tregs (xeno-Tregs) have become a promising immune therapy strategy to protect xenografts with fewer side effects. In this study, we aimed to identify an efficient and stable subset of xeno-Tregs. We enriched CD27+ xeno-Tregs using cell sorting and evaluated their suppressive functions and stability in vitro via mixed lymphocyte reaction (MLR), real-time polymerase chain reaction, inflammatory induction assay, and Western blotting...
2023: Cell Transplantation
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