Ep. 79: “ILC2s, the Microbiome, and Fibroblasts” Featuring Dr. Kellen Cavagnero
Jun 4, 2024
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Dr. Kellen Cavagnero, a Postdoctoral Fellow at UC San Diego, dives into the surprising role of fibroblasts in inflammatory conditions and their defense against staph infections. He sheds light on antimicrobial resistance and how these immune-acting fibroblasts can recruit neutrophils during inflammation. The conversation also touches on his podcast, Inflammatory Content, revealing his passion for science communication. Kellen emphasizes the need to rethink fibroblasts’ roles in immune responses, challenging long-held assumptions in immunology.
ILC2 cells play a crucial role in modulating adaptive immunity by interacting with the microbiome, especially through dietary fibers.
Recent studies advocating for functional antibody assays over traditional methods enhance malaria vaccine development by better predicting clinical immunity.
Advancements in engineered CAR T cell therapy showcase potential in eradicating HIV reservoirs, marking significant progress in treatment strategies.
Deep dives
Exploring ILC2 and the Microbiome
The discussion revolves around ILC2 cells and their role in immune responses, particularly how they interact with the microbiome, especially in the context of dietary fibers. It is noted that ILC2 cells help in responding to environmental changes and modulating adaptive immunity. The importance of these cells in maintaining a balanced immune system is emphasized, highlighting recent research that sheds light on their functionality and interactions. This exploration clarifies their contribution to homeostasis and how they could potentially be targeted for therapeutic interventions.
Challenges in Malaria Vaccine Development
The episode presents insights from a recent study focusing on improving malaria vaccine efficacy through innovative evaluation methods. It highlights the limitations of traditional growth inhibition assays in determining vaccine effectiveness, advocating for a shift towards functional antibody assays that provide a more comprehensive understanding of immune responses. The findings suggest that these functional assays better predict clinical immunity against malaria, thus offering a promising direction for future vaccine design. The study emphasizes the need for reliable measures to enhance the translational aspect of immunology.
Advancements in CAR T-Cell Therapy for HIV
A novel approach to treating HIV using engineered CAR T cells is discussed, particularly highlighting the M10 CAR T cells designed to target the viral reservoir. This research demonstrates the potential of doing more than just inhibiting the virus; by utilizing these modified cells, there is a possibility of eradicating the viral reservoir in patients. The multifaceted design of the CAR T cells, which includes producing broadly neutralizing antibodies and homing to infected B-cell follicles, signifies a breakthrough in HIV treatment. Initial trials show promise, suggesting significant suppression of viral rebound, thus marking a crucial step toward better therapeutic strategies for HIV.
Understanding Immune Dysregulation in Autoimmunity
The discussion delves into the genetic underpinnings of severe combined immunodeficiency (SCID) and Omen syndrome, linking specific mutations in the NUDCD3 gene to disrupted immune function. It highlights how this mutation interferes with critical processes in T and B cell development, leading to autoimmunity and heightened infection susceptibility. The research connects the dots between genetic variants and immune receptor recombination failures, providing a comprehensive view of the pathway leading to these syndromes. Such findings emphasize the importance of genomic studies in identifying the mechanisms of immune dysregulation.
Innovating Cancer Treatment Through Protein Degradation
Research presenting a new method for cancer treatment centers on the use of protacs to target RIPK1 for degradation, enhancing immunogenic cell death. This method exploits the body’s natural system to selectively degrade proteins to balance pro-survival and pro-apoptosis signals, potentiating immune responses against tumors. The approach shows promise in amplifying anti-tumor immunity by modulating necroptosis and inflammatory pathways, ultimately improving responses to existing therapies like radiation and immune checkpoint inhibitors. This innovative strategy suggests that targeted protein degradation could be a powerful tool in cancer immunotherapy.
Dr. Kellen Cavagnero is a Postdoctoral Fellow at the University of California, San Diego. His PhD work focused on how fibroblasts — a cell type thought to be immunologically inert — contribute to chronic inflammatory conditions and defense against pathogens. He talks about staph infections, antimicrobial resistance, and the types and roles of fibroblasts. He also discusses his work in science communication, including his podcast, Inflammatory Content.
Malaria Immunity – Scientists leveraged a human malaria infection study to investigate functional correlates of immunity.
CAR T Therapy for HIV – Anti-HIV-1 CAR-T cells armed with endogenic broadly neutralizing antibodies resulted in significant suppression of viral rebound in HIV patients.
Immunogenic Cell Death – Researchers generated a small-molecule proteolysis-targeting chimera that selectively degraded human and murine RIPK1.
Origins of Autoimmunity – NUDCD3 is required for healthy T and B cell development in humans.
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