Ep. 128: “Lymphatic Immunobiology” Featuring Dr. Amanda Lund
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In episode 128 of The Immunology Podcast, hosts Dr. Jason Goldsmith and Dr. Brenda Routt welcome Dr. Amanda Lund from NYU Grossman School of Medicine to explore the underappreciated role of lymphatic vasculature in immune function. The episode begins with a roundup of recent immunology research, including a groundbreaking study revealing that MHC class I on target cells regulates CD4 T cell-mediated immunity through ferroptosis, challenging the traditional view that NK cells are the primary responders to MHC-deficient cells. Another paper highlights intestinal epithelial cells expressing MHC class II as key initiators of CNS autoimmunity in models of multiple sclerosis, suggesting the gut-brain axis plays a central role in autoimmune disease. A third study presents an innovative in vivo CAR T-cell engineering platform using CRISPR and AAV vectors to generate functional CAR T cells directly in the body, offering a potentially cheaper, more scalable alternative to current ex vivo methods. The core of the episode focuses on Dr. Lund’s research, which reveals that lymphatic vessels are not passive conduits but active regulators of immunity. Using a vaccinia virus infection model, her team discovered that lymphatic capillaries 'zipper' shut post-infection, reducing fluid flow and sequestering pathogens—yet paradoxically enhancing adaptive immune responses by promoting dendritic cell migration and optimal antigen presentation. This dynamic behavior, influenced by interferon-gamma and metabolic state, suggests lymphatics can be 'tuned' to improve cancer immunotherapy by uncoupling beneficial immune activation from harmful metastasis. The conversation ends with Dr. Lund sharing her aspiration to write a non-scientific book, underscoring the creative parallels between science and storytelling.
Lymphatic vessels are not passive tubes but active regulators of immunity, capable of dynamically altering their permeability to control immune responses.
In tumor environments, lymphatic vessels can become dysfunctional and promote metastasis, but their state can be influenced by the tumor’s inflammatory environment and metabolic signals.
A novel in vivo CAR T-cell engineering approach using CRISPR and AAV vectors enables direct, site-specific gene editing in T cells within the body, potentially revolutionizing cancer immunotherapy.
Intestinal epithelial cells expressing MHC class II can initiate autoimmune responses in the CNS, highlighting the gut as a critical site for the origin of neuroinflammatory diseases.
Reduced MHC class I expression increases susceptibility to CD4 T cell-mediated ferroptosis, suggesting a new mechanism for tumor immune surveillance beyond NK cell recognition.
Introduction and Sponsorship: PBMC Isolation & Cytokine Samples
The episode opens with a welcome from hosts Dr. Jason Goldsmith and Dr. Brenda Routt, introducing the topic of lymphatic immunobiology. They highlight sponsorships from Stem Cell Technologies, promoting CEPMATE and Lymphoprep for streamlined PBMC isolation and offering free samples until May 11th. They also promote a free cytokine sample program until May 15th.
Immunology News Roundup: MHC-I, Autoimmunity & Gut-Brain Axis
“When you knock out MHC1, the GVHD is worse... it's at least interferon gamma driven. But then they look at all the... deep single cell RNA-seq and looking at pathways, and figure out that ferroptosis, iron-mediated killing, is driven up in MHC1 deficient cells with more lipid peroxidation as well.”
In Vivo CAR T-Cell Engineering: A New Frontier in Immunotherapy
“They show that they can generate CAR T cells in vivo at very high efficiency. I think they get up to like 50%, which is very impressive. Without having to take the cells out of the mice...”
Deep Dive with Dr. Amanda Lund: Lymphatic Vasculature as an Active Immune Regulator
“The lymphatics can really help to sort of direct or focus the information in a way that makes the immune system more functional in the lymph node. And that's not how I had thought about it originally.”
“The lymphatics can really help to sort of direct or focus the information in a way that makes the immune system more functional in the lymph node. And that's not how I had thought about it originally.”
“When you knock out MHC1, the GVHD is worse... it's at least interferon gamma driven. But then they look at all the... deep single cell RNA-seq and looking at pathways, and figure out that ferroptosis, iron-mediated killing, is driven up in MHC1 deficient cells with more lipid peroxidation as well.”
“They show that they can generate CAR T cells in vivo at very high efficiency. I think they get up to like 50%, which is very impressive. Without having to take the cells out of the mice...”
Hosts
Guest
Dr. Amanda Lund
person
CAR T-cells
other
CD4 T cells
other
Lymph Nodes
other
MHC Class I
other
Dendritic Cells
other
Lymphatic Capillaries
other
MHC Class II
other
CRISPR
other
NYU Grossman School of Medicine
organization
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