A5102980601- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Chemokine receptors and signaling
- Monoclonal and Polyclonal Antibodies Research
- Reproductive System and Pregnancy
- Reproductive Physiology in Livestock
- HIV Research and Treatment
- CAR-T cell therapy research
- Genetic and phenotypic traits in livestock
- Effects of Environmental Stressors on Livestock
- Respiratory viral infections research
- Pneumonia and Respiratory Infections
- Transgenic Plants and Applications
- Immunodeficiency and Autoimmune Disorders
- Chronic Lymphocytic Leukemia Research
- Systemic Lupus Erythematosus Research
- Mast cells and histamine
- Influenza Virus Research Studies
- IL-33, ST2, and ILC Pathways
- Viral Infectious Diseases and Gene Expression in Insects
- Cancer Immunotherapy and Biomarkers
- Estrogen and related hormone effects
- Reproductive Biology and Fertility
- Psoriasis: Treatment and Pathogenesis
The University of Adelaide
2012-2022
Rockefeller University
2017-2021
Centre for Cancer Biology
2014
Centre Val de Loire
2014
Biologie des Oiseaux et Aviculture
2012
Light- and dark-zone death dynamics Germinal centers (GCs) are areas within lymphoid organs where mature B cells expand differentiate during normal immune responses. GCs separated into two anatomic compartments: the dark zone, divide undergo somatic hypermutation, light they selected for affinity-enhancing mutations after interacting with T follicular helper cells. Mayer et al. studied apoptosis reporter mice found that both GC zones experience very high rates of (see Perspective by Bryant...
Abstract IL-17-producing helper T (Th17) cells are critical for host defense against extracellular pathogens but also drive numerous autoimmune diseases. Th17 that differ in their inflammatory potential have been described including IL-10-producing weak inducers of inflammation and highly inflammatory, IL-23-driven, GM-CSF/IFNγ-producing cells. However, distinct developmental requirements, functions trafficking mechanisms vivo remain poorly understood. Here we identify a temporally regulated...
Abstract Interleukin 17-producing γδ T (γδT17) cells have unconventional trafficking characteristics, residing in mucocutaneous tissues but also homing into inflamed via circulation. Despite being fundamental to γδT17-driven early protective immunity and exacerbation of autoimmunity cancer, migratory cues controlling γδT17 cell positioning barrier recruitment inflammatory sites are still unclear. Here we show that constitutively express chemokine receptors CCR6 CCR2. While recruits resting...
The discovery that humans can produce potent broadly neutralizing antibodies (bNAbs) to several different epitopes on the HIV-1 spike has reinvigorated efforts develop an antibody-based vaccine. Antibody cloning from single cells revealed nearly all bNAbs show unusual features could help explain why it not been possible elicit them by traditional vaccination and instead would require a sequence of immunogens. This idea is supported experiments with genetically modified immunoglobulin (Ig)...
Memory B cells comprise a heterogenous group of that differ in origin and phenotype. During the early phases immune response, activated can differentiate into IgM-expressing memory cells, short-lived plasma or seed germinal centers (GCs). The compartment is subsequently enriched by have been through several rounds division selection GC. Here, we report on use an unbiased lineage-tracking approach to explore origins properties cell subsets mice with intact system. We find continue throughout...
Antibody responses are characterized by increasing affinity and diversity over time. Affinity maturation occurs in germinal centers a mechanism that involves repeated cycles of somatic mutation selection. How antibody diversify while also undergoing is not as well understood. Here, we examined center (GC) dynamics tracking B cell entry, division, mutation, specificity. Our experiments show naive cells continuously enter GCs where they compete for T help undergo clonal expansion. Consistent...
Abstract Migration of Th cells to peripheral sites inflammation is essential for execution their effector function. The recently described Th9 subset characteristically produces IL-9 and has been implicated in both allergy autoimmunity. Despite this, the migratory properties remain enigmatic. In this study, we examined chemokine receptor usage by demonstrate, models autoimmunity, that these express functional CCR3, CCR6, CXCR3, receptors commonly associated with other, functionally opposed...
Significance The immune system relies on coordinated interactions between motile cells guided by molecules known as chemokines. However, processes that control chemokine distribution in complex vivo microenvironments are poorly understood. Dendritic barrier tissues require the CCL21 to enter lymphatic vessels during tissue egress. Here, we demonstrate ACKR4 shapes and prevents leakage of from tissue. Without ACKR4, extracellular gradients sites saturated nonfunctional, DCs cannot home...
Generating a pneumococcal vaccine that is serotype independent and cost effective remains global challenge. γ-Irradiation has been used widely to sterilize biological products. It can also be utilized as an inactivation technique generate whole-cell bacterial viral vaccines with minimal impact on pathogen structure antigenic determinants. In the present study, we γ-irradiation inactivate un-encapsulated Streptococcus pneumoniae strain Rx1 unmarked deletion of autolysin gene lytA pneumolysin...
Current immunotherapies involving CD8+ T cell responses show remarkable promise, but their efficacy in many solid tumors is limited, part due to the low frequency of tumor-specific cells tumor microenvironment (TME). Here, we identified a role for host atypical chemokine receptor 4 (ACKR4) controlling intratumor accumulation and activation. In absence ACKR4, an increase inhibited growth, nonhematopoietic ACKR4 expression was critical. We that CD103+ dendritic retention through regulation...
The CC‐chemokine receptor 6 (CCR6) is expressed constitutively at an intermediate level on naïve B cells and upregulated after activation pregerminal center (GC) cells. We hypothesized that it could be involved in the events leading to GC reaction high‐affinity antibody production, therefore investigated potential role of CCR6 B‐cell differentiation vivo . After antigenic challenge −/− mice with T‐cell‐dependent antigen nitrophenyl‐keyhole limpet hemocyanin (NP‐KLH), development was found...
The CC-chemokine receptor 6 (CCR6) can be detected on naive and activated B cells. Counterintuitively, its absence accelerates the appearance of germinal centres (GCs) increases production low-affinity antibodies. detailed mechanism CCR6 function during humoral response has remained elusive, but previously we identified a distinct CCR6high B-cell population in vivo early after antigenic challenge. In this study, defined specifically as early, pre-GC accordance, show that is upregulated...
Activated B cells can initially differentiate into three functionally distinct fates—early plasmablasts (PBs), germinal center (GC) cells, or early memory cells—by mechanisms that remain poorly understood. Here, we identify atypical chemokine receptor 4 (ACKR4), a decoy binds and degrades CCR7 ligands CCL19/CCL21, as regulator of activated cell differentiation. By restricting initial access to splenic interfollicular zones (IFZs), ACKR4 limits the proliferation reducing numbers available for...
Human anti-HIV-1 broadly neutralizing antibodies (bNAbs) protect against infection in animal models. However, bNAbs have not been elicited by vaccination diverse wild-type animals or humans, part because B cells expressing the precursors of these do recognize most HIV-1 envelopes (Envs). Immunogens designed that activate cell vivo, but they also competing off-target responses. Here we report on a complementary approach to expand specific using an anti-idiotypic antibody, iv8, selects for...
Streptococcus pneumoniae and influenza are the world's foremost bacterial viral respiratory pathogens. We have previously described a γ-irradiated A virus (γ-FLU) vaccine that provides cross-protective immunity against heterosubtypic infections. More recently, we reported novel non-adjuvanted S (γ-PN) elicits serotype-independent protection. Considering clinical synergism of both pathogens, combination pneumococcal with broad-spectrum to protect infections would considerable impact. In...
Crosstalk between T and B cells is crucial for generating high-affinity, class-switched antibody responses. The roles of CD4 + in this process have been well-characterised. In contrast, regulation responses by CD8 significantly less defined. are principally recognised eliciting cytotoxic peripheral tissues forming protective memory. However, recent findings identified a novel population effector that co-opt differentiation program characteristic follicular helper (Tfh) cells, upregulate the...
The class IB phosphoinositide 3-kinase gamma enzyme complex (PI3Kγ) functions in multiple signaling pathways involved leukocyte activation and migration, making it an attractive target human inflammatory diseases including MS. Here, using pik3cg−/− mice a selective PI3Kγ inhibitor, we show that promotes development of experimental autoimmune encephalomyelitis (EAE). In mice, EAE is markedly suppressed fewer leukocytes CD4+ CD8+ T cells, granulocytes mononuclear phagocytes infiltrate the CNS....
T‐cell selection and development occurs as precursor cells journey through the thymus interact with stromal residing in distinct microenvironments. Although chemokines CCL19, CCL21, CCL25 CXCL12 are known to have major roles intrathymic migration of thymocytes thymocyte precursors, significance other such CCL20, which is also expressed thymus, unknown. This particular interest given that location natural regulatory (nTreg) population CCL20 receptor CCR6 has an important role peripheral...