Browsing by Author "Cannon, Anthony M."

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    Case Studies of Sustained Remission of Membranous Glomerulonephritis With Dupilumab Treatment
    (Elsevier, 2024-10-10) Kaplan, Mark H.; Greco, Jessica M.; Rovin, Brad H.; Cannon, Anthony M.; Pajulas, Abigail; Travers, Jeffrey B.; Hallab, Ayman; Turner, Matthew J.; Microbiology and Immunology, School of Medicine
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    Mast cells interact directly with colorectal cancer cells to promote epithelial-to-mesenchymal transition
    (bioRxiv, 2025-03-19) Lanzloth, Rosie; Harris, Nicole L.; Cannon, Anthony M.; Kaplan, Mark H.; O’Hagan, Heather M.; Microbiology and Immunology, School of Medicine
    Mast cells (MCs), a type of granulocytic immune cell, can be both pro- and anti-tumorigenic in colorectal cancer (CRC). We hypothesized that these contrasting findings may be in part due to differential interactions of MCs with CRC subtypes. BRAF mutant CRC uniquely contains intestinal secretory cell types. In this study, we demonstrated that MCs are enriched in BRAF mutant CRC, likely because they are recruited by factors released from cancer secretory cells. To investigate the functional consequences of MC-CRC cell interactions, we performed direct coculture experiments. We demonstrated that MCs promote epithelial-to-mesenchymal transition (EMT) in CRC cells in a calcium- and contact-dependent fashion. Furthermore, inhibiting LFA-1 and ICAM1 integrin binding reduced the coculture-induced EMT-related marker expression in CRC cells. The MC-CRC cell interaction facilitates the transfer of biological materials, including mRNA molecules, from MCs to CRC cells. This study is the first to report a contact-dependent, pro-tumorigenic role of MCs in CRC, as well as the transfer of molecules encoded by MCs to CRC cells. These findings enhance our comprehension of cell-cell communication between immune and cancer cells. Furthermore, this work suggests that targeting MC-CRC interactions, particularly through modulating integrin pathways, could offer new therapeutic strategies for aggressive CRC subtypes.
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    TL1A priming induces a multi-cytokine Th9 cell phenotype that promotes robust allergic inflammation in murine models of asthma
    (Elsevier, 2024) Niese, Michelle L.; Pajulas, Abigail L.; Rostron, Cameron R.; Cheung, Cherry C. L.; Krishnan, Maya S.; Zhang, Jilu; Cannon, Anthony M.; Kaplan, Mark H.; Microbiology and Immunology, School of Medicine
    Multi-cytokine-producing Th9 cells secrete IL-9 and type 2 cytokines and mediate mouse and human allergic inflammation. However, the cytokines that promote a multi-cytokine secreting phenotype have not been defined. Tumor necrosis factor superfamily member TL1A signals through its receptor DR3 to increase IL-9. Here we demonstrate that TL1A increases expression of IL-9 and IL-13 co-expressing cells in murine Th9 cell cultures, inducing a multi-cytokine phenotype. Mechanistically, this is linked to histone modifications allowing for increased accessibility at the Il9 and Il13 loci. We further show that TL1A alters the transcription factor network underlying expression of IL-9 and IL-13 in Th9 cells and increases binding of transcription factors to Il9 and Il13 loci. TL1A-priming enhances the pathogenicity of Th9 cells in murine models of allergic airway disease through the increased expression of IL-9 and IL-13. Lastly, in both chronic and memory-recall models of allergic airway disease, blockade of TL1A signaling decreases the multi-cytokine Th9 cell population and attenuates the allergic phenotype. Taken together, these data demonstrate that TL1A promotes the development of multi-cytokine Th9 cells that drive allergic airway diseases and that targeting pathogenic T helper cell-promoting cytokines could be an effective approach for modifying disease.