A5067302232- Ocular Diseases and Behçet’s Syndrome
- Systemic Lupus Erythematosus Research
- interferon and immune responses
- T-cell and B-cell Immunology
- Psoriasis: Treatment and Pathogenesis
- Cytomegalovirus and herpesvirus research
- Cytokine Signaling Pathways and Interactions
- Immune Response and Inflammation
- Immunotherapy and Immune Responses
- Neuroinflammation and Neurodegeneration Mechanisms
- Dermatology and Skin Diseases
- Urticaria and Related Conditions
- Immune Cell Function and Interaction
- Immunodeficiency and Autoimmune Disorders
- Mosquito-borne diseases and control
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- IL-33, ST2, and ILC Pathways
- Inflammasome and immune disorders
- Tryptophan and brain disorders
- Otitis Media and Relapsing Polychondritis
- HIV Research and Treatment
- CRISPR and Genetic Engineering
- Viral Infections and Vectors
- Macrophage Migration Inhibitory Factor
- Complement system in diseases
National Institutes of Health
2015-2025
National Eye Institute
2015-2024
National Institute of Allergy and Infectious Diseases
2015
Oregon Health & Science University
2013
National Institute of Immunology
1998-1999
We noted an unexpected inheritance pattern of lesions in several strains gene-manipulated mice with ocular phenotypes. The lesions, which appeared at various stages backcross to C57BL/6, bore resemblance the rd8 retinal degeneration phenotype. set out examine prevalence this mutation induced mutant mouse lines, vendor C57BL/6 and widely used embryonic stem cells.Ocular were evaluated by fundus examination histopathology. Detection genetic level was performed PCR appropriate primers. Data...
Considerable progress has been made in testing stem cell-derived retinal pigment epithelium (RPE) as a potential therapy for age-related macular degeneration (AMD). However, the recent reports of oncogenic mutations induced pluripotent cells (iPSCs) underlie need robust manufacturing and functional validation clinical-grade iPSC-derived RPE before transplantation. Here, we developed mutation-free iPSCs from three AMD patients differentiated them into iPSC-RPE patches on biodegradable...
Abstract Interleukin 35 (IL-35) is a heterodimeric cytokine composed of IL-12p35 and Ebi3 subunits. IL-35 suppresses autoimmune diseases while preventing host defense to infection promoting tumor growth metastasis by converting resting B T cells into IL-10-producing IL-35-producing regulatory (Breg) (Treg) cells. Despite sharing the subunit, IL-12 (IL-12p35/IL-12p40) promotes inflammatory responses whereas (IL-12p35/Ebi3) induces responses, suggesting that may have unknown intrinsic...
Abstract Structural and functional homologies between the Zika Dengue viruses’ envelope proteins raise possibility that cross-reactive antibodies induced following virus infection might enhance subsequent infection. Using rhesus macaque model we show prior with leads to a significant enhancement of Dengue-2 viremia is accompanied by neutropenia, lympocytosis, hyperglycemia, higher reticulocyte counts, along activation pro-inflammatory monocyte subsets release inflammatory mediators....
Abstract Immune privilege is used by the eye, brain, reproductive organs, and gut to preserve structural functional integrity in face of inflammation. The eye arguably most vulnerable and, therefore, also “privileged” tissues; paradoxically, it remains subject destructive autoimmunity. It has been proposed, although never proven vivo, that can induce T regulatory cells (Tregs) locally. Using Foxp3-GFP reporter mice expressing a retina-specific TCR, we now show uncommitted rapidly convert...
IFN-γ is a pathogenic cytokine involved in inflammation. Paradoxically, its deficiency exacerbates experimental autoimmune encephalomyelitis, uveitis, and arthritis. Here, we demonstrate using IFN-γ−/− mice repleted with IFN-γ+/+ NK cells that innate production of from necessary sufficient to trigger an endogenous regulatory circuit limits autoimmunity. After immunization, DCs recruited IFN-γ-producing the draining lymph node interacted them CXCR3-dependent fashion. The interaction caused...
Regulatory B cells (Breg cells) that secrete IL-10 or IL-35 (i35-Breg) play key roles in regulating immunity tumor microenvironment during autoimmune and infectious diseases. Thus, loss of Breg function is implicated development diseases while aberrant elevation prevents sterilizing immunity, exacerbates diseases, promotes cancer metastasis. identified thus far are largely antigen-specific derive mainly from B2-lymphocyte lineage. Here, we describe an innate-like IL-27–producing natural...
To test the hypothesis that ROSAH (retinal dystrophy, optic nerve oedema, splenomegaly, anhidrosis and headache) syndrome, caused by dominant mutation in
Experimental autoimmune uveitis (EAU) is a disease of the neural retina induced by immunization with retinal antigens, such as interphotoreceptor retinoid-binding protein (IRBP) and arrestin (retinal soluble antigen, S-Ag). EAU serves model for human uveitic diseases associated major histocompatibility complex (HLA) genes, in which patients exhibit immunological responses to antigens. Here we report development humanized HLA transgenic (TG) mice. HLA-DR3, -DR4, -DQ6, -DQ8 TG mice were...
Abstract Acute SIV infection is characterized by explosive of memory CD4 T cells in peripheral and mucosal tissues. Interestingly, relatively few are infected until as late days 7–8 after challenge. However, day 10 postinfection, most the carry viral DNA. The rapidity with which expands within 2–3 to encompass virtually entire cell compartment suggests significant alterations susceptibility during this period. mechanism(s) underlying increased permissiveness not known. In study, we show that...
Abstract Functional macrophage heterogeneity is well appreciated outside the CNS in wound healing and cancer, was recently also demonstrated several compartments after “sterile” insults. Yet, such largely overlooked context of inflammatory autoimmune pathology, which macrophages were mainly associated with disease induction propagation. In this article, we show diversity monocyte-derived along course experimental uveitis, an condition affecting ocular system, serving as a model for...
SUMMARY Despite ocular immune privilege, circulating retina-specific T cells can trigger autoimmune uveitis, yet intraocular bleeding-a relatively common event-rarely leads to disease. Using an in vivo privilege model, we previously reported that all naive entering the eye become primed situ; about 30% Foxp3+ T-regulatory (Tregs), while rest fail induce pathology. Here, single-cell transcriptomics and functional validation revealed distinct phenotypes both populations: Tregs were highly...
Commensals shape host physiology through molecular crosstalk with receptors. Identifying specific microbial factors that causally influence immunity is key to understanding homeostasis at the host-microbe interface and advancing microbial-based therapeutics. Here, we identify trehalose monocorynomycolate (TMCM) from Corynebacterium mastitidis ( C. mast ) as a potent stimulator of IL-17 production by γδ T cells ocular surface. Mechanistically, TMCM-driven responses require both IL-1 signals...
Immunologically privileged retinal antigens can serve as targets of experimental autoimmune uveitis (EAU), a model for human uveitis. The tolerance status susceptible strains, whose target antigen is not expressed in the thymus at detectable levels, unclear. Here, we address this issue directly by analyzing consequences genetic deficiency versus sufficiency uveitogenic antigen, interphotoreceptor retinoid-binding protein (IRBP). IRBP-knockout (KO) and wild-type (WT) mice on highly...
The eye is an immunologically privileged and profoundly immunosuppressive environment. Early studies reported inhibition of T cell proliferation, IFN-γ production, generation regulatory cells (Tregs) by aqueous humor (AH) identified TGF-β as a critical factor. However, subsets including Foxp3(+) Treg Th17 were unknown at that time, was the role retinoic acid (RA) in induction. Consequently, effect ocular microenvironment on lineage commitment function, RA this process, had not been explored....
Multiple sclerosis (MS) is an inflammatory demyelinating disease in which cytokines produced by immune cells that infiltrate the brain and spinal cord play a central role. We show here IL-12p35, alpha subunit of IL-12 or IL-35 cytokine, might be effective biologic for suppressing neuroinflammatory responses ameliorating pathology experimental autoimmune encephalomyelitis (EAE), mouse model human MS. further IL-12p35 conferred protection from neuropathy inhibiting expansion pathogenic Th17...
Purpose: Experimental autoimmune uveitis (EAU) induced in mice using the retinal antigen interphotoreceptor retinoid binding protein (IRBP) is an animal model for posterior humans. However, EAU by native IRBP or its widely used epitope amino acid residues 1 to 20 of human (hIRBP1-20) inconsistent, often showing low scores and incidence. We found urgent need identify a better pathogenic C57BL/6 strain. Methods: Mice were immunized with uveitogenic peptides bovine IRBP. Clinical histological...
Uveitis is a potentially sight-threatening disease characterized by repeated cycles of remission and recurrent inflammation. The JAK/STAT pathway regulates the differentiation pathogenic Th1 Th17 cells that mediate uveitis. A SOCS1 mimetic peptide (SOCS1-KIR) inhibits JAK2/STAT1 pathways has recently been shown to suppress experimental autoimmune uveitis (EAU). However, it not clear whether SOCS1-KIR ameliorated targeting lymphocytes or via inhibition macrophages antigen-presenting also...
Alzheimer's disease (AD) is the leading cause of dementia worldwide, but there are limited therapeutic options and no current cure. While involvement microglia in AD has been highly appreciated, role other innate adaptive immune cells remains largely unknown, partly due to their scarcity heterogeneity. This study aimed non-microglial wild type AD-transgenic mouse brains across different ages. Our results uncovered presence a unique CD8+ T cell population that were selectively increased aging...
purpose. Interphotoreceptor retinoid binding protein (IRBP) is the major uveitogenic retinal antigen eliciting experimental autoimmune uveoretinitis (EAU) in mice. The most frequently used mouse strains are B10.RIII and C57BL/6, but to date only one epitope for each has been identified. purpose of this study was identify characterize additional epitopes C57BL/6 mice compare recognition wild-type versus IRBP-deficient on both backgrounds. methods. Mice were immunized with IRBP. Spleen cells...