Here is a sampling of our work
T Helper 1 Cellular Immunity Toward Recoverin Is Enhanced in Patients With Active Autoimmune Retinopathy.
This study is a result of our lab’s multi-year collaboration with Dr. John Heckenlively and Dr. Thiran Jayasundera in the Retinal Dystrophy Clinic of the Kellogg Eye Center. In it we compared the immune profiles and reactivity toward the retinal antigen recoverin in patients with diagnosed autoimmune retinopathy, retinitis pigmentosa and control subjects with no vision loss. The major finding was that the Th1 branch of the immune system was activated in the AIR patients by recoverin suggesting that AIR is a cell-mediated autoimmune disease.
Differential influence on regulatory B cells by th2 cytokines affects protection in allergic airway disease.
This article published in Aug. 2018 in the Journal of Immunology shows that the allergy-associated cytokines IL-4 and IL-5 have different effects on growth and function of regulatory CD5+ B lymphocytes. IL-5 is an inducer of regulatory B cell IL-10 production while IL-4 blocks this function. The transfer of IL-5-stimulated B cells into mice preconditioned to have allergic airway inflammation caused a decrease in several parameters of disease.
The editors of Frontiers in Immunology asked us to write this focused review as a follow up to our article demonstrating the production of FasL+ exosomes by B lymphoblastoid cell lines. In the review, we explore the connection of these findings to previous work on killer B cells in mouse models and the therapeutic potential of killer B cells and their exosomes.
This article published March 1, 2016 in the journal Neurology: Neuroimmunology and Neuroinflammation (N2) demonstrates that regulatory B lymphocytes increase in number in MS patients after treatment with BG-12. It is part of an ongoing collaboration between my lab and the group led by Yang Mao-Draayer in the Department of Neurology at the Univerisity of Michigan.
Human B Cell-Derived Lymphoblastoid Cell Lines Constitutively Produce Fas Ligand and Secrete MHCII(+)FasL(+) Killer Exosomes.
This study shows that intracellular Fas ligand expression is common among EBV-transformed B lymphoblastoid cell lines, and is released in the form of FasL+MHCII+ exosomes that have killer activity against activated TH cells.
This paper resulted from a collaboration between our lab and the labs of Terry Smith (U. Mich) and Claus Nielsen (Copenhagen U. Denmark. It describes differences in regulatory B cell populations that were found in thyroiditis patients and control subjects.
Antitumor effector B cells directly kill tumor cells via the Fas/FasL pathway and are regulated by IL-10.
This research article is from a collaboration with scientists in the University of Michigan Cancer Center. It details the use of tumor-draining lymph node-derived B cells as direct killers of mouse breast tumor cells. The activity of these killer B cells was enhanced in IL-10 knockout mice.
This review article gives a comprehensive overview of the current literature regarding immune suppression by B cells circa 2011. It also discusses the possibility of multi-potent suppressor B cell subset.
This review article summarizes the literature pertaining to death ligand expression by B cells and highlights some potential uses of killer B cells in fighting diseases.
This invited chapter in a book dedicated to protocols for analyzing regulatory B cells, details some of our methods for working with FasL+ killer B cells
Chronic schistosome infection leads to modulation of granuloma formation and systemic immune suppression
This review article discusses the role of schistosome worms in shaping the immune response. Emphasis is on regulatory T and B lymphocytes and how deworming may lead to increases in proinflammatory diseases.
This study explores the connection between arthritis severity and Fas-ligand expressing B cells.
This study of cockroach allergen-induced asthma in B-1a cell deficient XID mice demonstrated that lung inflammation, Th1 and Th2 cytokine production and T cell apoptosis were all regulated by B-1a cells. Particularily striking was the complete lack of lung T cell death in XID mice compared to wild type mice.
Fas Ligand-Expressing B-1a Lymphocytes Mediate CD4+-T-Cell Apoptosis during Schistosomal Infection: Induction by Interleukin 4 (IL-4) and IL-10
This study showed that CD5+ B cells constitutively expressed Fas ligand and were very sensitive through stimulation with schistosome egg antigen, IL-4 and IL-10 to express high levels of FasL. These 'regulatory' B-1a cells were potent stimulators of antigen-specific T cell death.
Soluble egg antigen-stimulated T helper lymphocyte apoptosis and evidence for cell death mediated by FasL+ T and B cells during murine Schistosoma mansoni infection
This article was our first study showing that B cells express Fas ligand and are involved in mediating T cell apoptosis. This data laid the groundwork for our current studies on regulatory antigen presentation in autoimmunity.
Attenuation of allergen-induced responses in CCR6-/- mice is dependent upon altered pulmonary T lymphocyte activation.
This was a follow-up study to determine the mechanism of resistance of CCR6-/- mice to cockroach-allergen induced asthma. By using adoptive transfer of CCR6+/+ T cells to CCR6-/- mice, it was shown that wild-type T cells produced more IL-5 upon antigen challenge. This led to increased lung eosinophilia and serum IgE production. A defect in APCs was also detected in CCR6-/- mice.
Interleukin-12-independent down-modulation of cockroach antigen-induced asthma in mice by intranasal exposure to bacterial lipopolysaccharide.
In this study, we explored the mechanisms involved in LPS-induced suppression of airway hypersensitivity in the cockroach allergen model. Contrary to the expectation that it was caused by a skew in T cell response toward Th1-type, blocking of IL-12 did not change the outcome.
This review article gives a detailed description of what was known about the role played by Th17 cells in diverse human diseases in 2008.
This review article highlights our current understanding of the importance of T cells to the pathophysiology of joint inflammation in RA. Particular emphasis is placed on recent evidence from spontaneous arthritis models, interactions between T cells and classical and non-classical antigen presenting cells, and on the emerging role of Th17 cells in RA.
This review highlights the cellular communications in inflamed arthritic joints. Special emphasis is given to new targets of treatment based on these interactions.
This review article explores the phenotypic characteristics of synovial T cells and their interactions with fibroblast-like synoviocytes, B cells, macrophages and dendritic cells of the synovium.
This article documents the interaction of cytokine-activated T cells with FLS using time-lapse microscopy. These interactions led to the production of IL-6 and IL-8 by FLS that was dependent on surface TNF alpha expressed by Tck, and which was complemented by IL-17.
This study demonstrated that RA-FLS lines could present antigenic peptides T cell hybridoma lines. It was a continuation of previous work that showed the ability of FLS to mediate superantigenic T cell stimulation.
Divergence of the systemic immune response following oral infection with distinct strains of Porphyromonas gingivalis.
This research article resulted from studies done in collaboration with Julie Marchesan and William Giannobile in the UM Dental School. The oral microbe P. gingivalis has effects on the systemic immune system that may contribute to arthritis development.
Porphyromonas gingivalis oral infection exacerbates the development and severity of collagen-induced arthritis.
This was a collaborative research project led by Julie Marchesan, who earned her Ph.D. in the lab of William Giannobile in the U of M Dental School.
This study was done in collaboration with Dr. Michal Olszewski in the VA Ann Arbor Health System, and Liise-Anne Pirofsky at the Albert Einstein College of Medicine in the Bronx, NY
This article is a product of our ongoing collaboration with the laboratory of Michael Mayer in the Biomedical Engineering Department. Using the IonWorks instrument developed by Essen Instruments of Ann Arbor, Michigan, it was demonstrated that the potassium channel, Kv1.3, has increased activity following T cell activation. This has important implications to autoimmune diseases since this K+ channel has been found to be highly active on effector memory T cells.
Paper describing the role of CD5+ B cells in a major kidney disease of humans. Collaboration with Tan Jinquan of Wuhan University in Wuhan, China.
This study showed that CD8+ T cells are important contributors to the Type 2 cytokine response in the cockroach-antigen asthma model.
Soluble egg antigens from Schistosoma mansoni induce angiogenesis-related processes by up-regulating vascular endothelial growth factor in human endothelial cells.
12(S)-hydroxyeicosatetraenoic acid and 13(S)-hydroxyoctadecadienoic acid regulation of protein kinase C-alpha in melanoma cells: role of receptor-mediated hydrolysis of inositol phospholipids.
Eosinophil-active cytokine from mononuclear cells cultured with L-tryptophan products: an unexpected consequence of endotoxin contamination.
Restrictions in the repertoire of allospecific T cells. Contribution of the alpha-helical sequence polymorphism of HLA-DR molecules.
3-(Phenylamino)alanine, a novel aniline-derived amino acid associated with the eosinophilia-myalgia syndrome: a link to the toxic oil syndrome?