Life Sciences Commons^™

The Investigations Of Nps Modulated Immunity And Immunometabolism, Brittney Leigh Ruedlinger

Biomedical Sciences Theses & Dissertations

Cancers remain in the top noncommunicable diseases responsible for premature mortality. The heterogeneity among cancers and within tumors makes treating them ever more challenging. Our misfortune for developing cures is mocked by cancer, with the lowest probability of success (PoS) through clinical trials and FDA approval. At the basic level, there are generally two broad gaps impeding cancer eradication: the unidentified shared mechanism(s) exploited by all cancers and the therapeutic approach to intervene. Nanosecond pulse stimulation (NPS) offers a unique approach since its broad impacts intersect those often hijacked by oncogenesis. Metabolic pathways, known for dysfunctions among cancers, share a …

Efficacy Of Sediment Contaminant Remediation Of The Benthos In A Segment Of The Southern Branch Of The Elizabeth River, Colton Martin

Biological Sciences Theses & Dissertations

The bottom sediment of the Southern Branch of the Elizabeth River, a tributary of Chesapeake Bay, was historically contaminated with hydrocarbons from industrial sources especially wood treatment facilities. The Elizabeth River Project selected a section of the bottom off Money Point in the Southern Branch for a sediment contaminant remediation effort. Prior to initiation of remediation efforts, a survey occurred in summer 2010 to characterize the ecological condition of the benthic communities off Money Point compared to benthic communities of a benthic region across the channel and northwest of Money Point near Blows Creek. That study characterized the benthos of …

Overfishing Drives Over One-Third Of All Sharks And Rays Toward A Global Extinction Crisis, Nicholas K. Dulvy, Nathan Pacoureau, Cassandra L. Rigby, Riley A. Pollom, Rima W. Jabado, David A. Ebert, Brittany Finucci, Caroline M. Pollock, Jessica Cheok, Danielle H. Derrick, Katelyn B. Herman, C. Samantha Sherman, Wade J. Vanderwright, Julia M. Lawson, Rachel H.L. Walls, John K. Carlson, Patricia Charvet, Kinattumkara K. Bineesh, Daniel Fernando, Gina M. Ralph, Jay H. Matsushiba, Craig Hilton-Taylor, Sonja V. Fordham, Colin A. Simpfendorfer

Biological Sciences Faculty Publications

The scale and drivers of marine biodiversity loss are being revealed by the International Union for Conservation of Nature (IUCN) Red List assessment process. We present the first global reassessment of 1,199 species in Class Chondrichthyes-sharks, rays, and chimeras. The first global assessment (in 2014) concluded that one-quarter (24%) of species were threatened. Now, 391 (32.6%) species are threatened with extinction. When this percentage of threat is applied to Data Deficient species, more than one-third (37.5%) of chondrichthyans are estimated to be threatened, with much of this change resulting from new information. Three species are Critically Endangered (Possibly Extinct), representing …

Examining Melt Pond Dynamics And Light Availability In The Arctic Ocean Via High Resolution Satellite Imagery, Austin Wesley Abbott

OES Theses and Dissertations

As the Arctic experiences consequences of climate change, a shift from thicker, multi-year ice to thinner, first-year ice has been observed. First-year ice is prone to extensive pools of meltwater (“melt ponds”) forming on its surface, which enhance light transmission to the ocean. Changes in the timing and distribution of melt pond formation and associated increases in under-ice light availability are the primary drivers for seasonal progression of water column primary production and warming. Observations of melt pond development and distribution require meter scale resolution and have traditionally been limited to airborne images. However, recent advances in high spatial resolution …

The Impact Of Nanopulse Treatment On The Tumor Microenvironment In Breast Cancer: Overturning The Treg Immunosuppressive Dominance, Anthony Nanajian

Biomedical Sciences Theses & Dissertations

Nanopulse treatment (NPT) is a high-power electric engineering modality that has been shown to be an effective local tumor treatment approach in multiple cancer models. Our previous studies on the orthotopic 4T1-luc breast cancer model demonstrated that NPT ablated local tumors. The treatment consequently conferred protection against a second live tumor challenge and minimized spontaneous metastasis. This study aims to understand how NPT mounts a potent immune response in a predominantly immunosuppressive tumor.

NPT changed the local and systemic dynamics of immunosuppressive cells by significantly reducing the numbers of regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages …

Anaplasma Phagocytophilum Modulates Mammalian And Arthropod Signaling For Its Survival And Transmission, Supreet Khanal

Biomedical Sciences Theses & Dissertations

Vector-borne diseases (VBDs) are illnesses transmitted to humans and other animals by arthropods such as ticks, mosquitoes, and fleas. These arthropod vectors transmit infectious pathogens such as viruses, bacteria, and protozoa, to humans during blood-feeding. We have very few control strategies to treat or control these diseases. Human anaplasmosis, caused by the bacterium Anaplasma phagocytophilum, is the second most common tick-borne disease in the United States. This work defines three studies elucidating Anaplasma phagocytophilum-mediated modulation of cell signaling in mammalian cells and arthropod vector Ixodes scapularis ticks.

The first study focused on mammalian PI3 kinases signaling in regulating …

Moderate Heat-Assisted Gene Electrotransfer For Intradermal Dna Vaccination And Protein Replacement Therapy In The Skin, Chelsea Marie Edelblute

Biomedical Sciences Theses & Dissertations

Gene electrotransfer (GET) holds great promise for the delivery of therapeutic agents. The skin serves as an attractive target for GET due to its availability and unique cellular composition. Protein replacement therapy and DNA vaccination are potential applications for intradermal GET. The combination of moderate tissue preheating and GET has been shown to achieve elevated gene expression levels while reducing the necessary applied voltage. In the current work, we utilized a 16-pin multi-electrode array (MEA) and incorporated nine optical fibers, connected to an infrared laser, to pre-heat the tissue to 43°C before application of GET. In a guinea pig model, …

Determination Of The Presence Of Rickettsia Spp. And Borrelia Spp. Carried By Tortoise Ticks From Madagascar, Anna Phan

Biological Sciences Theses & Dissertations

Ticks were removed from three species of Malagasy tortoises, Astrochelys yniphora, A. radiata, and Pyxis arachnoides (comprising two subspecies P. a. arachnoides and P. a. oblonga), between 2012 and 2015. The ticks were presumed to be from the genus Amblyomma. Ticks were morphologically identified and then checked molecularly to confirm their classification or identify any ticks that could not be morphologically identified. Molecular identification was done via end-point PCR that amplified tick cytochrome oxidase (CO1) and tick 12S rRNA genes. Ticks were screened via a real-time polymerase chain reaction assay for the presence of Rickettsia spp. …

The Role Of Backreef Soundscapes And Their Spatial Structure For Recruitment Of Tropical Marine Larvae, Emily R. Anderson

Biological Sciences Theses & Dissertations

Underwater sound is a cue used by many marine larvae to orient to coastal habitats including backreef, sponge-dominated hardbottom habitat in the Florida Keys (Florida, USA) – a particularly “noisy” coastal habitat. However, the distance over which acoustic cues are attractive to settlement-stage larvae - is generally unknown. I examined this phenomenon in a region of the Florida Keys where mass sponge die-offs have diminished both underwater soundscapes and larval settlement. The absence of pronounced hardbottom-associated sound over such a large area allowed me to experimentally test in situ the response of fish and invertebrate larvae to broadcasted sounds at …

The Effects Of Urbanization On Plant Biodiversity In Southeastern Virginia, Tess Hardesty

Undergraduate Research Symposium

This research project investigated the impacts of urbanization on plant species biodiversity within Southeastern Virginia. The hypothesized results of this research were if there was an increase in urbanization, then plant diversity would decrease. Plant biodiversity can increase the decomposition rates, pollination success, and biomass production of the area. Decreasing in plant biodiversity can increase the spread of pathogens through plant populations and increase herbivore damage. There was data compiled from SERNEC herbarium records of four counties, Accomack, Northampton, Norfolk, and Virginia Beach. Virginia Beach had the largest population increase, which was considered the measurement for urbanization in this study. …

Diet Of Long-Eared Owl And Common Kestrel In An Urban Landscape (Ukraine), Ivan Zahorodnyi, Oleksii Dubovyk, Ivan Komarnytskyi, Ihor Dykyy

Biological Sciences Faculty Publications

In the present study we performed a comparative dietary analysis of two predatory birds, the Long-eared Owl (Asio otus) and the Common Kestrel (Falco tinnunculus) in the district of Lviv city. We found that the Long-eared Owl and the Common Kestrel are typical small mammal specialists within the urban ecosystem. Considering the abundance and biomass of prey, small mammals comprise 98.4% of the Long-eared Owl’s diet. The species composition of mammals coincides almost 50% in the food intake comparison of the two birds. It has been established that the main prey of both species is the …

Antibodies Against Egf-Like Domains In Ixodes Scapularis Bm86 Orthologs Impact Tick Feeding And Survival Of Borrelia Burgdorferi, Juraj Koči, Sandhya Bista, Payal Chirania, Xiuli Yang, Chrysoula Kitsou, Vipin Singh Rana, Ozlem Buyuktanir Yas, Daniel E. Sonenshine, Utpal Pal

Biological Sciences Faculty Publications

Ixodes scapularis ticks transmit multiple pathogens, including Borrelia burgdorferi sensu stricto, and encode many proteins harboring epidermal growth factor (EGF)-like domains. We show that I. scapularis produces multiple orthologs for Bm86, a widely studied tick gut protein considered as a target of an anti-tick vaccine, herein termed as Is86. We show that Is86 antigens feature at least three identifiable regions harboring EGF-like domains (termed as EGF-1, EGF-2, and EGF-3) and are differentially upregulated during B. burgdorferi infection. Although the RNA interference-mediated knockdown of Is86 genes did not show any influences on tick engorgement or B. burgdorferi sensu stricto persistence, the …

Spatio-Temporal Modelling Of Tick Life-Stage Count Data With Spatially Varying Coefficients, Thabo Lephoto, Henry Mwambi, Oliver Bodhlyera, Holly Gaff

Biological Sciences Faculty Publications

There is a vast amount of geo-referenced data in many fields of study including ecological studies. Geo-referencing is usually by point referencing; that is, latitudes and longitudes or by areal referencing, which includes districts, counties, states, provinces and other administrative units. The availability of large geo-referenced datasets for modelling has necessitated the development and application of spatial statistical methods. However, spatial varying coefficients models exploring the abundance of tick counts remain limited. In this study we used data that was collected and prepared by researchers in the Department of Biological Sciences from the Old Dominion University, Virginia, USA. We modelled …

Focus Stacking Images Of Morphological Character States For Differentiating The Adults Of Ixodes Affinis And Ixodes Scapularis (Acari: Ixodidae) In Areas Of Sympatry, Robyn M. Nadolny, Marcée Toliver, Holly D. Gaff, John G. Snodgrass, Richard G. Robbins

Biological Sciences Faculty Publications

Adult females and males of Ixodes affinis and Ixodes scapularis are illustrated by focus stacking image photography, and morphological character states are described that reliably differentiate the two species. In conjunction with other environmental cues, such as the questing phenology of adults, these characteristics will enable the rapid identification of adults of either sex along the southern Coastal Plain of the United States, where these species are sympatric.

Polar Bear Behavior: Morphologic And Physiologic Adaptations, John P. Whiteman

Biological Sciences Faculty Publications

Polar bears possess morphologic and physiologic characteristics that reflect their terrestrial lineage as members of the bear family (Ursidae) as well as adaptations to the Arctic marine environment. Among marine mammals, they are the least adapted for aquatic life. They exhibit substantial seasonality in body mass, body condition, and many physiological functions, reflecting the annual cycle of both their Arctic sea ice habitat and the availability of their main prey, ringed seals. This hypercarnivorous diet has likely influenced the polar bear’s craniodental morphology and nutritional physiology. Similar to other marine mammal predators, polar bears exhibit a relatively high resting metabolic …

Remarkably High And Consistent Tolerance Of A Red Sea Coral To Acute And Chronic Thermal Stress Exposures, Nicolas R. Evensen, Maoz Fine, Gabriela Perna, Christian R. Voolstra, Daniel J. Barshis

Biological Sciences Faculty Publications

Global warming is resulting in unprecedented levels of coral mortality due to mass bleaching events and, more recently, marine heatwaves, where rapid increases in seawater temperature cause mortality within days. Here, we compare the response of a ubiquitous scleractinian coral, Stylophora pistillata, from the northern Red Sea to acute (7 h) and chronic (7-11 d) thermal stress events that include temperature treatments of 27 degrees C (i.e., the local maximum monthly mean), 29.5 degrees C, 32 degrees C, and 34.5 degrees C, and assess recovery of the corals following exposure. Overall, S. pistillata exhibited remarkably similar responses to acute …

Dietary Protein Content And Digestibility Influences Discrimination Of Amino Acid Nitrogen Isotope Values In A Terrestrial Omnivorous Mammal, John P. Whiteman, Mauriel Rodriguez Curras, Kelli L. Feeser, Seth D. Newsome

Biological Sciences Faculty Publications

RATIONALE: Ecologists increasingly determine the δ¹⁵N values of amino acids (AA) in animal tissue; "source" AA typically exhibit minor variation between diet and consumer, while "trophic" AA have increased δ¹⁵N values in consumers. Thus, trophic-source δ¹⁵N offsets (i.e., Δ¹⁵N_T-S) reflect trophic position in a food web. However, even minor variation in δ¹⁵N_{source AA} values may influence the magnitude of offset that represents a trophic step, known as the trophic discrimination factor (i.e., TDF_T-S). Diet digestibility and protein content can influence the δ¹⁵N values …

Trends And Opportunities In Tick-Borne Disease Geography, Catherine A. Lippi, Sadie J. Ryan, Alexis L. White, Holly D. Gaff, Colin J. Carlson

Biological Sciences Faculty Publications

Tick-borne diseases are a growing problem in many parts of the world, and their surveillance and control touch on challenging issues in medical entomology, agricultural health, veterinary medicine, and biosecurity. Spatial approaches can be used to synthesize the data generated by integrative One Health surveillance systems, and help stakeholders, managers, and medical geographers understand the current and future distribution of risk. Here, we performed a systematic review of over 8,000 studies and identified a total of 303 scientific publications that map tick-borne diseases using data on vectors, pathogens, and hosts (including wildlife, livestock, and human cases). We find that the …

Response Of Fish And Invertebrate Larvae To Backreef Sounds At Varying Distances: Implications For Habitat Restoration, Emily R. Anderson, Jack Butler, Mark J. Butler

Biological Sciences Faculty Publications

Underwater sound is used by many marine larvae to orient to coastal habitats including backreef, sponge-dominated hardbottom habitat in the Florida Keys (FL, United States)—a particularly “noisy” coastal habitat. However, the distance over which acoustic cues are attractive to settlement-stage larvae is generally unknown. We examined this phenomenon in a region of the Florida Keys where mass sponge die-offs have diminished both underwater soundscapes and larval settlement. The absence of pronounced hardbottom-associated sound over such a large area allowed us to experimentally test in situ the response of fish and invertebrate larvae to broadcasted sounds at different distances from their …

Global Extinction Risk For Seahorses, Pipefishes And Their Near Relatives (Syngnathiformes), Riley A. Pollom, Gina M. Ralph, Caroline M. Pollock, Amanda C.J. Vincent

Biological Sciences Faculty Publications

Few marine taxa have been comprehensively assessed for their conservation status, despite heavy pressures from fishing, habitat degradation and climate change. Here we report on the first global assessment of extinction risk for 300 species of syngnathiform fishes known as of 2017, using the IUCN Red List criteria. This order of bony teleosts is dominated by seahorses, pipefishes and seadragons (family Syngnathidae). It also includes trumpetfishes (Aulostomidae), shrimpfishes (Centriscidae), cornetfishes (Fistulariidae) and ghost pipefishes (Solenostomidae). At least 6% are threatened, but data suggest a mid-point estimate of 7.9% and an upper bound of 38%. Most of the threatened species are …

Tick Ecdysteroid Hormone, Global Microbiota/Rickettsia Signaling In The Ovary Versus Carcass During Vitellogenesis In Part-Fed (Virgin) American Dog Ticks, Dermacentor Variabilis, Loganathan Ponnusamy, Haley Sutton, Robert D. Mitchell Iii, Daniel E. Sonenshine, Charles S. Apperson, Richard Michael Roe

Biological Sciences Faculty Publications

The transovarial transmission of tick-borne bacterial pathogens is an important mechanism for their maintenance in natural populations and transmission, causing disease in humans and animals. The mechanism for this transmission and the possible role of tick hormones facilitating this process have never been studied. Injections of physiological levels of the tick hormone, 20-hydroxyecdysone (20E), into part-fed (virgin) adult females of the American dog tick, Dermacentor variabilis, attached to the host caused a reduction in density of Rickettsia montanensis in the carcass and an increase in the ovaries compared to buffer-injected controls. This injection initiates yolk protein synthesis and uptake …

Complete Genome Sequence Of Rickettsia Parkeri Strain Black Gap, Sandor E. Karpathy, Christopher D. Paddock, Stephanie L. Grizzard, Dhwani Batra, Lori A. Rowe, David T. Gauthier

Biological Sciences Faculty Publications

A unique genotype of Rickettsia parkeri, designated R. parkeri strain Black Gap, has thus far been associated exclusively with the North American tick, Dermacentor parumapertus. The compete genome consists of a single circular chromosome with 1,329,522 bp and a G+C content of 32.5%.

Effects Of Weather On Foraging Success And Hunting Frequency In Winter-Irruptive Snowy Owls (Bubo Scandiacus) In Upstate New York, Russell E. Winter, William M. Shields

Biological Sciences Faculty Publications

The effects of weather on an individual can often alter the population dynamics of a species. Knowledge of how weather influences individual behavior is therefore essential in understanding its full impact in the context of population ecology. Snowy Owls (Bubo scandiacus) exhibit expensive long-distance migrations in winters following population irruptions. During irruptive movements, many owls migrate past the southernmost extent of their traditional wintering grounds, the mechanism for which is still debated. We propose and test the “milder climate” hypothesis; Snowy Owls wintering in lower latitudes are better able to meet their metabolic demands due to higher temperatures …

Variation In Coral Thermotolerance Across A Pollution Gradient Erodes As Coral Symbionts Shift To More Heat-Tolerant Genera, Melissa S. Naugle, Thomas A. Oliver, Daniel J. Barshis, Ruth D. Gates, Cheryl A. Logan

Biological Sciences Faculty Publications

Phenotypic plasticity is one mechanism whereby species may cope with stressful environmental changes associated with climate change. Reef building corals present a good model for studying phenotypic plasticity because they have experienced rapid climate-driven declines in recent decades (within a single generation of many corals), often with differential survival among individuals during heat stress. Underlying differences in thermotolerance may be driven by differences in baseline levels of environmental stress, including pollution stress. To examine this possibility, acute heat stress experiments were conducted on Acropora hyacinthus from 10 sites around Tutuila, American Samoa with differing nutrient pollution impact. A threshold-based heat …

Tick Extracellular Vesicles Enable Arthropod Feeding And Promote Distinct Outcomes Of Bacterial Infection, Adela S. Oliva Chávez, Xiaowei Wang, Liron Marnin, Nathan K. Archer, Holly L. Hammond, Erin E. Mcclure Carroll, Dana K. Shaw, Brenden G. Tully, Amanda D. Buskirk, Shelby L. Ford, L. Rainer Butler, Preeti Shahi, Kateryna Morozova, Cristina C. Clement, Lauren Lawres, Anya J. O'Neal, Choukri Ben Mamoun, Kathleen L. Mason, Brandi E. Hobbs, Glen A. Scoles, Eileen M. Barry, Daniel E. Sonenshine, Utpal Pal, Jesus G. Valenzuela, Marcelo B. Sztein, Marcela F. Pasetti, Michael L. Levin, Michail Kotsyfakis, Steven M. Jay, Jason F. Huntley, Lloyd S. Miller, Laura Santambrogio, Joao H.F. Pedra

Biological Sciences Faculty Publications

Extracellular vesicles are thought to facilitate pathogen transmission from arthropods to humans and other animals. Here, we reveal that pathogen spreading from arthropods to the mammalian host is multifaceted. Extracellular vesicles from Ixodes scapularis enable tick feeding and promote infection of the mildly virulent rickettsial agent Anaplasma phagocytophilum through the SNARE proteins Vamp33 and Synaptobrevin 2 and dendritic epidermal T cells. However, extracellular vesicles from the tick Dermacentor andersoni mitigate microbial spreading caused by the lethal pathogen Francisella tularensis. Collectively, we establish that tick extracellular vesicles foster distinct outcomes of bacterial infection and assist in vector feeding by acting …

Double Anus In An Ixodes Scapularis Nymph, A Medically Important Tick Vector, Vikas Taank, Frank A. Lattanzio, Hameeda Sultana, Girish Neelakanta

Biological Sciences Faculty Publications

Background: Ixodes scapularis ticks are medically important arthropod vectors that transmit several pathogens to humans. The observations of morphological abnormalities, including nanism, missing leg, extra leg, and gynandromorphism, have been reported in these ticks. In this study, we report the presence of two anuses in a laboratory-reared I. scapularis nymph.

Results: Larval ticks were allowed to feed on mice and to molt to nymphs. Two anuses were observed in one of the freshly molted nymphs. Stereo and scanning electron microscopy confirmed the presence of two anuses in one nymph within a single anal groove.

Conclusions: This report confirms the rare …

Fast And Pervasive Transcriptomic Resilience And Acclimation Of Extremely Heat-Tolerant Coral Holobionts From The Northern Red Sea, Romain Savary, Daniel J. Barshis, Christian R. Voolstra, Anny Cárdenas, Nicolas R. Evensen, Guilhem Banc-Prandi, Maoz Fine, Anders Meiborn

Biological Sciences Faculty Publications

Corals from the northern Red Sea and Gulf of Aqaba exhibit extreme thermal tolerance. To examine the underlying gene expression dynamics, we exposed Stylophora pistillata from the Gulf of Aqaba to short-term (hours) and long-term (weeks) heat stress with peak seawater temperatures ranging from their maximum monthly mean of 27 °C (baseline) to 29.5 °C, 32 °C, and 34.5 °C. Corals were sampled at the end of the heat stress as well as after a recovery period at baseline temperature. Changes in coral host and symbiotic algal gene expression were determined via RNA-sequencing (RNA-Seq). Shifts in coral microbiome composition were …

Patterns Of Genetic Divergence Across Geographically Variable Populations Of Xanthisma Gracile (Asteraceae), Lavanya Challagundla, Lisa E. Wallace

Biological Sciences Faculty Publications

Premise of research. Numerous biotic and abiotic factors can contribute to local selection and lead to geographic structure and genetic divergence between populations. The southwestern United States contains many distinctive plant communities, ranging from woodlands to desert scrub, that are shaped by species adapting to local variation in elevation, precipitation, seasonality, and soils. Given this variation, species occurring across diverse habitats are expected to harbor high genetic diversity and exhibit significant genetic differences associated with environmental variation.

Methodology. Here, we studied the genetic divergence of populations of Xanthisma gracile (Asteraceae) across Arizona using amplified fragment length polymorphisms and evaluated associations …

Consensus Guidelines For Advancing Coral Holobiont Genome And Specimen Voucher Deposition, Christian R. Voolstra, Kate M. Quigley, Sarah W. Davies, John Everett Parkinson, Raquel S. Peixoto, Manuel Aranda, Andrew C. Baker, Adam R. Barno, Daniel J. Barshis, Francesca Benzoni, Victor Bonito, David G. Bourne, Carol Buitrago-López, Tom C.L. Bridge, Cheong Xin Chan, David J. Combosch, Jamie Craggs, Jörg C. Frommlet, Santiago Herrera, Andrea M. Quattrini, Till Röthig, James D. Reimer, Esther Rubio-Portillo, David J. Suggett, Helena Villela, Maren Ziegler, Michael Sweet

Biological Sciences Faculty Publications

Coral research is being ushered into the genomic era. To fully capitalize on the potential discoveries from this genomic revolution, the rapidly increasing number of high-quality genomes requires effective pairing with rigorous taxonomic characterizations of specimens and the contextualization of their ecological relevance. However, to date there is no formal framework that genomicists, taxonomists, and coral scientists can collectively use to systematically acquire and link these data. Spurred by the recently announced “Coral symbiosis sensitivity to environmental change hub” under the “Aquatic Symbiosis Genomics Project” - a collaboration between the Wellcome Sanger Institute and the Gordon and Betty Moore Foundation …

Self And Microbiota-Derived Epitopes Induce Cd4⁺ T Cell Anergy And Conversion Into Cd4⁺Foxp3⁺ Regulatory Cells, Michal P. Kuczma, Edyta A. Szurek, Anna Cebula, Vu L. Ngo, Maciej Pietrzak, Piotr Kraj, Timothy L. Denning, Leszek Ignatowicz

Biological Sciences Faculty Publications

The physiological role of T cell anergy induction as a key mechanism supporting self-tolerance remains undefined, and natural antigens that induce anergy are largely unknown. In this report, we used TCR sequencing to show that the recruitment of CD4⁺CD44⁺Foxp3⁻CD73⁺FR4⁺ anergic (Tan) cells expands the CD4⁺Foxp3⁺ (Tregs) repertoire. Next, we report that blockade in peripherally-induced Tregs (pTregs) formation due to mutation in CNS1 region of Foxp3 or chronic exposure to a selecting self-peptide result in an accumulation of Tan cells. Finally, we show that microbial antigens from Akkermansia muciniphila …