All Publications

  • Combining RNA in situ hybridization and spectral flow cytometry to investigate the leukocyte glycocalyx in autoimmunity Marshall, P. L., Kaber, G., Linde, M. H., Barlow, G. L., Haddock, N. L., Wagar, L., Nagy, N., Bollyky, P. L. AMER ASSOC IMMUNOLOGISTS. 2020
  • Reprogramming leukemia cells into antigen presenting cells as a novel cancer vaccination immunotherapy Linde, M. H., Dove, C. G., Gurev, S. F., Phan, P., Zhao, F., Gars, E. J., Marshall, P. L., Miller, L. P., Majeti, R. AMER ASSOC IMMUNOLOGISTS. 2020
  • Pericellular hyaluronan modulates IL-2 responsiveness through CD44 Martinez, H., Marshall, P. L., Kaber, G., Nagy, N., Bollyky, P. L. AMER ASSOC IMMUNOLOGISTS. 2020
  • Hyaluronan synthesis inhibition impairs antigen presentation and delays transplantation rejection. Matrix biology : journal of the International Society for Matrix Biology Marshall, P. L., Nagy, N. n., Kaber, G. n., Barlow, G. L., Ramesh, A. n., Xie, B. J., Linde, M. H., Haddock, N. L., Lester, C. A., Tran, Q. L., de Vries, C. n., Hargil, A. n., Malkovskiy, A. n., Gurevich, I. n., Martinez, H. A., Kuipers, H. F., Yadava, K. n., Zhang, X. n., Evanko, S. P., Gebe, J. A., Wang, X. n., Vernon, R. B., de la Motte, C. n., Wight, T. N., Engleman, E. G., Krams, S. M., Meyer, E. n., Bollyky, P. L. 2020


    A coat of pericellular hyaluronan surrounds mature dendritic cells (DC) and contributes to cell-cell interactions. We asked whether 4-methylumbelliferone (4MU), an oral inhibitor of HA synthesis, could inhibit antigen presentation. We find that 4MU treatment reduces pericellular hyaluronan, destabilizes interactions between DC and T-cells, and prevents T-cell proliferation in vitro and in vivo. These effects were observed only when 4MU was added prior to initial antigen presentation but not later, consistent with 4MU-mediated inhibition of de novo antigenic responses. Building on these findings, we find that 4MU delays rejection of allogeneic pancreatic islet transplant and allogeneic cardiac transplants in mice and suppresses allogeneic T-cell activation in human mixed lymphocyte reactions. We conclude that 4MU, an approved drug, may have benefit as an adjunctive agent to delay transplantation rejection.

    View details for DOI 10.1016/j.matbio.2020.12.001

    View details for PubMedID 33290836

  • 4-Methylumbelliferyl glucuronide contributes to hyaluronan synthesis inhibition JOURNAL OF BIOLOGICAL CHEMISTRY Nagy, N., Gurevich, I., Kuipers, H. F., Ruppert, S. M., Marshall, P. L., Xie, B. J., Sun, W., Malkovskiy, A. V., Rajadas, J., Grandoch, M., Fischer, J. W., Frymoyer, A. R., Kaber, G., Bollyky, P. L. 2019; 294 (19): 7864–77
  • Hyaluronan in immune dysregulation and autoimmune diseases MATRIX BIOLOGY Nagy, N., Kuipers, H. F., Marshall, P. L., Wang, E., Kaber, G., Bollyky, P. L. 2019; 78-79: 292–313
  • Bacteriophage trigger antiviral immunity and prevent clearance of bacterial infection SCIENCE Sweere, J. M., Van Belleghem, J. D., Ishak, H., Bach, M. S., Popescu, M., Sunkari, V., Kaber, G., Manasherob, R., Suh, G. A., Cao, X., de Vries, C. R., Lam, D. N., Marshall, P. L., Birukova, M., Katznelson, E., Lazzareschi, D. V., Balaji, S., Keswani, S. G., Hawn, T. R., Secor, P. R., Bollyky, P. L. 2019; 363 (6434): 1416-+
  • Modified High-Molecular-Weight Hyaluronan Promotes Allergen-Specific Immune Tolerance AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY Gebe, J. A., Yadava, K., Ruppert, S. M., Marshall, P., Hill, P., Falk, B. A., Sweere, J. M., Han, H., Kaber, G., Medina, C., Mikecz, K., Ziegler, S. F., Balaji, S., Keswani, S. G., Perez, V. A., Butte, M. J., Nadeau, K., Altemeier, W. A., Fanger, N., Bollyky, P. L. 2017; 56 (1): 109-120


    The extracellular matrix in asthmatic lungs contains abundant low-molecular-weight hyaluronan, and this is known to promote antigen presentation and allergic responses. Conversely, high-molecular-weight hyaluronan (HMW-HA), typical of uninflamed tissues, is known to suppress inflammation. We investigated whether HMW-HA can be adapted to promote tolerance to airway allergens. HMW-HA was thiolated to prevent its catabolism and was tethered to allergens via thiol linkages. This platform, which we call "XHA," delivers antigenic payloads in the context of antiinflammatory costimulation. Allergen/XHA was administered intranasally to mice that had been sensitized previously to these allergens. XHA prevents allergic airway inflammation in mice sensitized previously to either ovalbumin or cockroach proteins. Allergen/XHA treatment reduced inflammatory cell counts, airway hyperresponsiveness, allergen-specific IgE, and T helper type 2 cell cytokine production in comparison with allergen alone. These effects were allergen specific and IL-10 dependent. They were durable for weeks after the last challenge, providing a substantial advantage over the current desensitization protocols. Mechanistically, XHA promoted CD44-dependent inhibition of nuclear factor-κB signaling, diminished dendritic cell maturation, and reduced the induction of allergen-specific CD4 T-helper responses. XHA and other potential strategies that target CD44 are promising alternatives for the treatment of asthma and allergic sinusitis.

    View details for DOI 10.1165/rcmb.2016-0111OC

    View details for Web of Science ID 000392133000012

    View details for PubMedCentralID PMC5248962