A5061618672- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- IL-33, ST2, and ILC Pathways
- Transplantation: Methods and Outcomes
- Eosinophilic Esophagitis
- Immunotherapy and Immune Responses
- Asthma and respiratory diseases
- Psoriasis: Treatment and Pathogenesis
- Immunodeficiency and Autoimmune Disorders
- Whipple's Disease and Interleukins
- Pneumocystis jirovecii pneumonia detection and treatment
- Polyomavirus and related diseases
- CAR-T cell therapy research
- Toxin Mechanisms and Immunotoxins
- Dermatology and Skin Diseases
- Organ Transplantation Techniques and Outcomes
- Immune Response and Inflammation
- Neuroscience of respiration and sleep
- Ion Channels and Receptors
- Cytokine Signaling Pathways and Interactions
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Reconstructive Facial Surgery Techniques
- Cytomegalovirus and herpesvirus research
- Proteoglycans and glycosaminoglycans research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Brigham and Women's Hospital
2014-2023
Harvard University
2013-2022
Broad Institute
2021-2022
Biogen (United States)
2020
Society of Thoracic Surgeons
2018
Moscow Research and Clinical Center for Neuropsychiatry
2018
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
2016
Kingston University
2015
University of California, San Francisco
2004-2006
University of Chicago
2001-2004
The high affinity interleukin (IL)-15 receptor, IL-15Rα, is essential for supporting lymphoid homeostasis. To assess whether IL-15Rα's role in vivo to trans present IL-15, we generated mixed bone marrow chimera from IL-15Rα– and IL-2/15Rβ–deficient mice. We find that IL-15Rα–competent, cells are able support IL-15Rα–deficient natural killer (NK) memory CD8+ T cells, thus ruling out secondary signals on these demonstrating IL-15Rα–mediated presentation of IL-15 the primary mechanism by which...
Natural killer (NK) cells protect hosts against viral pathogens and transformed cells. IL-15 is thought to play a critical role in NK cell development, but its the regulation of peripheral less well defined. We now find that adoptive transfer normal into mice lacking high affinity interleukin (IL)-15 receptor, IL-15Rα, surprisingly results abrupt loss these Moreover, IL-15Rα–deficient can differentiate successfully radiation bone marrow chimera bearing Finally, adoptively transferred survive...
Abstract NK cells protect hosts against viral pathogens and transformed cells, dendritic (DCs) play important roles in activating cells. We now find that murine IL-15Rα-deficient DCs fail to support cell cytolytic activity elaboration of IFN-γ, despite the fact these express normal levels costimulatory molecules IL-12. By contrast, IL-15Rα expression on is entirely dispensable for their activation by DCs. In addition, blockade with anti-IL-15Rα anti-IL-2Rβ but not anti-IL-2Rα-specific Abs...
Asthma is a chronic inflammatory disease that fails to resolve. Recently, key role for type 2 innate lymphoid cells (ILC2s) was linked asthma pathogenesis; however, mechanisms ILC2 regulation remain be determined. In this study, metabololipidomics of murine lungs identified temporal changes in endogenous maresin 1 (MaR1) during self-limited allergic inflammation. Exogenous MaR1 reduced lung inflammation and expression IL-5 IL-13 increased amphiregulin. augmented de novo generation regulatory...
Interleukin-27 (IL-27) is an immunoregulatory cytokine that suppresses inflammation through multiple mechanisms, including induction of IL-10, but the transcriptional network mediating its diverse functions remains unclear. Combining temporal RNA profiling with computational algorithms, we predict 79 transcription factors induced by IL-27 in T cells. We validate 11 known and discover 5 positive (Cebpb, Fosl2, Tbx21, Hlx, Atf3) 2 negative (Irf9 Irf8) Il10 regulators, generating experimentally...
Cytokine driven or “bystander” proliferation of T cells occurs in vivo independently major histocompatibility complex–T cell receptor interactions. This process may be important for supporting homeostasis and facilitating responses to microbial antigens, involve the cytokine interleukin (IL)-15. In this study, we find that IL-15Rα–deficient (IL-15Rα−/−) mice fail undergo poly I:C IL-15 bystander CD8+ cells. Surprisingly, IL-15Rα−/− proliferate response when adoptively transferred into normal...
The generation and maintenance of immunological memory requires the activation, expansion, persistent proliferation antigen-specific T cells. Recent work suggests that IL-15 may be important for this process. Surprisingly, we now find expression high-affinity receptor IL-15, IL-15Rα, on cells is dispensable or CD8 + By contrast, IL-15Rα other than absolutely critical function. These findings related to IL-15Rα's ability present in trans low-affinity IL-15Rβ/γ c receptors unexpected results...
Myeloid differentiation primary response protein 88 (MyD88) is classically known as an adaptor, linking TLR and IL-1R to downstream signaling pathways in the innate immune system. In addition its role cells, MyD88 has been shown play important T cells. How regulates helper T-cell remains largely unknown, however. Here we demonstrate that regulator of IL-17-producing CD4 + cells (Th17) cell proliferation. MyD88-deficient showed a defect Th17 differentiation, but not Th1 or Th2...
Podoplanin (PDPN, also known as Gp38) is highly expressed on the surface of lymphatic endothelial cells, where it regulates development vessels. We have recently observed that PDPN effector T cells infiltrate target tissues during autoimmune inflammation; however, function in largely unclear. Here, we demonstrated global deletion Pdpn results exaggerated cell responses and spontaneous experimental encephalomyelitis (EAE) mice with a susceptible genetic background. In contrast, cell-specific...
Matrix metalloproteinase-9 (MMP-9) cleaves various proteins to regulate inflammatory and injury responses. However, MMP-9's activities during influenza A viral (IAV) infections are incompletely understood. Herein, plasma MMP-9 levels were increased in patients with pandemic H1N1 seasonal IAV infections. lung localized airway epithelial cells leukocytes H1N1-infected WT murine lungs. Mmp-9-/- mice had lower mortality rates, reduced weight loss, titers, injury, along E-cadherin shedding...