Main Questions & Topics of Interest
- Neuroimmunology of Alzheimer’s disease.
Our lab’s research in the Neuroimmunology of Alzheimer’s disease centers on the role of γδ T cells in neuroinflammation and its contribution to the progression of neurodegenerative diseases. Alzheimer’s disease (AD) is increasingly understood to involve complex interactions between the nervous and immune systems, where γδ T cells appear to play a critical role in modulating the brain’s immune response. These unique T cells interact with microglia, the brain’s resident immune cells, and are believed to drive inflammation that may accelerate neurodegeneration.
We utilize advanced techniques in mouse models of AD and examine human AD brain tissues to understand how γδ T cells contribute to immune cell activation, particularly influencing other key immune players such as CD8+ T cells. By elucidating the signaling pathways and molecular interactions through which γδ T cells affect microglial function and neurodegenerative pathology, our research aims to uncover potential immune mechanisms that exacerbate AD pathology.
Through these insights, we hope to identify novel immunotherapeutic targets and pave the way for treatments that mitigate the harmful neuroimmune responses implicated in Alzheimer’s, potentially altering the course of this devastating disease.
- Maternal-Fetal Interactions in Gut-Brain Development and their Implications for neurodivergence
Our lab is deeply engaged in understanding the critical and complex role of maternal-fetal interactions in shaping both gut and brain development, with a focus on how maternal microbiota-derived metabolites influence the developing fetal brain and intestine. These microbial metabolites, which cross the placenta and reach the fetus, play an essential role in early developmental processes, influencing neural circuit formation, brain structure, and the establishment of a healthy gut barrier.
In particular, we are interested in how specific microbial metabolites affect neurodevelopmental pathways that are foundational to healthy brain function and how these pathways may, if disrupted, contribute to neurodivergent outcomes. The fetal gut and brain undergo concurrent development, and signals from maternal microbiota are hypothesized to synchronize these processes, preparing the neonate for coordinated brain-gut functionality after birth.
Our research combines animal models and cutting-edge analytical techniques to explore the mechanisms by which maternal microbial signals interact with fetal developmental pathways. This work seeks to reveal how early-life microbial exposure might shape lifelong neurological and intestinal health, offering valuable insights for early detection and potential interventions in neurodevelopmental disorders. Through this research, we aim to contribute to a better understanding of the maternal influences on fetal health and the origins of neurodivergence.
Relevant Publications:
Cox LM, Tatematsu BK, Guo L, LeServe DS, Mayrink J, Oliveira MG, Donnelly D, Fonseca RC, Lemos L, Lanser TB, Rosa AC, Lopes JR, Schwerdtfeger LA, Ribeiro GFC, Lobo ELC, Moreira TG, Oliveira AG, Weiner HL, Rezende RM. Gamma-delta T cells suppress microbial metabolites that activate striatal neurons and induce repetitive/compulsive behavior in mice. Brain Behav Immun. 2024
Lopes JR, Zhang X, Mayrink J, Tatematsu BK, Guo L, LeServe DS, Abou-El-Hassan H, Rong F, Dalton MJ, Oliveira MG, Lanser TB, Liu L, Butovsky O, Rezende RM, Weiner HL. Nasal administration of anti-CD3 monoclonal antibody ameliorates disease in a mouse model of Alzheimer’s disease. Proc Natl Acad Sci. 2023
Abou-El-Hassan H, Rezende RM, Izzy S, Gabriely G, Yahya T, Tatematsu BK, Habashy KJ, Lopes JR, de Oliveira GLV, Maghzi AH, Yin Z, Cox LM, Krishnan R, Butovsky O, Weiner HL.Vγ1 and Vγ4 gamma-delta T cells play opposing roles in the immunopathology of traumatic brain injury in males. Nat Commun. 2023
Rezende RM, Cox LM, Moreira TG, Liu S, Boulenouar S, Dhang F, LeServe DS, Nakagaki BN, Lopes JR, Tatematsu BK, Lemos L, Mayrink J, Lobo ELC, Guo L, Oliveira MG, Kuhn C, Weiner HL. Gamma-delta T cells modulate the microbiota and fecal micro-RNAs to maintain mucosal tolerance. Microbiome. 2023
Liu S, Rezende RM, Moreira TG, Tankou SK, Cox LM, Wu M, Song A, Dhang FH, Wei Z, Costamagna G, Weiner HL. Oral Administration of miR-30d from Feces of MS Patients Suppresses MS-like Symptoms in Mice by Expanding Akkermansia muciniphila. Cell Host Microbe. 2019
Rezende RM, Nakagaki BN, Moreira TG, Lopes JR, Kuhn C, Tatematsu BK, Boulenouar S, Maghzi AH, Rubino S, Menezes GB, Chitnis T, Weiner HL. γδ T Cell-Secreted XCL1 Mediates Anti-CD3-Induced Oral Tolerance. J Immunol. 2019
Rezende RM, Lanser AJ, Rubino S, Kuhn C, Skillin N, Moreira TG, Liu S, Gabriely G, David BA, Menezes GB, Weiner HL. γδ T cells control humoral immune response by inducing T follicular helper cell differentiation. Nat Commun. 2018
Liu S, da Cunha AP, Rezende RM, Cialic R, Wei Z, Bry L, Comstock LE, Gandhi R, Weiner HL. The Host Shapes the Gut Microbiota via Fecal MicroRNA. Cell Host Microbe. 2016
Rezende RM, da Cunha AP, Kuhn C, Rubino S, M’Hamdi H, Gabriely G, Vandeventer T, Liu S, Cialic R, Pinheiro-Rosa N, Oliveira RP, Gaublomme JT, Obholzer N, Kozubek J, Pochet N, Faria AMC, Weiner HL. Identification and characterization of latency-associated peptide-expressing γδ T cells. Nat Commun. 2015