Biology subjects

Lopez, D. A.

Publications and source records attributed to Lopez, D. A..

4 recordsLinked to original sources

bioRxiv2023

Prenatal inflammation reprograms hyperactive ILC2s that promote allergic lung inflammation and airway dysfunction

Allergic asthma is a chronic respiratory disease that initiates in early life, but causal mechanisms are poorly understood. Here we examined how prenatal inflammation shapes allergic asthma susceptibility by reprogramming lung immunity from early development. Induction of Type I interferon-mediated inflammation during development provoked expansion and hyperactivation of group 2 innate lymphoid cells (ILC2s) seeding the developing lung. Hyperactivated ILC2s produced increased IL-5 and IL-13, and were associated with acute Th2 bias, eosinophilia, and decreased Tregs in the lung. The hyperactive ILC2 phenotype was recapitulated by adoptive transfer of a fetal liver precursor following exposure to prenatal inflammation, indicative of developmental programming. Programming of ILC2 function and subsequent lung immune remodeling by prenatal inflammation led to airway dysfunction at baseline and in response to papain, indicating increased asthma susceptibility. Our data provide a link by which developmental programming of progenitors by early-life inflammation drives lung immune remodeling and asthma susceptibility through hyperactivation of lung-resident ILC2s. One Sentence SummaryPrenatal inflammation programs asthma susceptibility by inducing the production of hyperactivated ILC2s in the developing lung.

immunology↗

bioRxiv2022

Fetal hematopoietic stem cells are activated during acute prenatal infection with Toxoplasma gondii and IFNγ

Infection directly influences adult hematopoietic stem cell (HSC) function and differentiation, but much less is known about the fetal hematopoietic response to infection during pregnancy. Here, we investigated the fetal hematopoietic response to maternal infection with Toxoplasma gondii (T. gondii), an intracellular parasite that elicits Type II IFN{gamma}-mediated maternal immunity. The effects of maternal IFN{gamma} on developing HSCs and the signals that mediate these interactions have not been investigated. Our investigation reveals that the fetal HSCs respond to T. gondii infection with virulence-dependent changes in proliferation, self-renewal potential, and lineage output. We demonstrate that maternal IFN{gamma} crosses the fetal-maternal interface and is perceived by fetal HSCs. By comparing the effects of maternal IFN{gamma} injection with maternal T. gondii infection, our observations reveal that IFN{gamma} mimics aspects of the fetal HSC response to infection. Moreover, our data disentangle the role of infection-induced inflammatory cytokines in driving the expansion of downstream hematopoietic progenitors. Our findings illuminate that the fetal HSC response to prenatal infection is distinct from the adult HSC response to IFN{gamma}-induced inflammation.

immunology↗

bioRxiv2022

Prenatal inflammation perturbs fetal hematopoietic development and causes persistent changes to postnatal immunity

Adult hematopoietic stem and progenitor cells (HSPCs) respond directly to inflammation and infection, resulting in both acute and persistent changes to quiescence, mobilization, and differentiation. Here we show that fetal HSPCs respond to prenatal inflammation in utero, and that the fetal response shapes postnatal hematopoiesis and immunity. Heterogenous fetal HSPCs showed divergent responses to maternal immune activation (MIA), including changes in quiescence, expansion, and lineage-biased output. Single cell transcriptomic analysis of fetal HSPCs in response to MIA revealed specific upregulation of inflammatory gene profiles in discrete, transient HSC populations, that propagated expansion of lymphoid-biased progenitors. Beyond fetal development, MIA caused the inappropriate expansion and persistence of fetal lymphoid-biased progenitors postnatally, concomitant with increased cellularity and hyperresponsiveness of fetal-derived innate-like lymphocytes. Our investigation demonstrates how inflammation in utero can direct the trajectory of output and function of fetal-derived immune cells by reshaping fetal HSC establishment.

cell biology↗

bioRxiv2020

Meaningful Effects in the Adolescent Brain Cognitive Development Study

The Adolescent Brain Cognitive Development (ABCD) Study is the largest single-cohort prospective longitudinal study of neurodevelopment and childrens health in the United States. A cohort of n= 11,880 children aged 9-10 years (and their parents/guardians) were recruited across 22 sites and are being followed with in-person visits on an annual basis for at least 10 years. The study approximates the US population on several key sociodemographic variables, including sex, race, ethnicity, household income, and parental education. Data collected include assessments of health, mental health, substance use, culture and environment and neurocognition, as well as geocoded exposures, structural and functional magnetic resonance imaging (MRI), and whole-genome genotyping. Here, we describe the ABCD Study aims and design, as well as issues surrounding estimation of meaningful associations using its data, including population inferences, hypothesis testing, power and precision, control of covariates, interpretation of associations, and recommended best practices for reproducible research, analytical procedures and reporting of results.

neuroscience↗