Costimulatory Molecules for Immunomodulation to Enhance Immunity
Abstract
With advancement in identification of T cell subsets and advent of novel immunotherapeutics, costimulatory/inhibitory molecules have been attractive targets for researchers and clinicians. Costimulatory molecules are diverse, sometimes redundant, but effectuate T cell responses to steer potency and memory formation. Sialophorin has been implicated in cell trafficking, malignancy, co-stimulation/inhibition, receptor of pathogens, and apoptosis. Despite sialophorin is expressed on all T cells, glycosylation seems integral for many of its functions. In our study, we found that in contrast to established dogma, glycosylated sialophorin preferentially retained on memory type 17 T cells in mouse models and humans. Using mouse model of vaccine immunity, we show a non-redundant role of CD43 for type 17 cell responses. Vaccine immunity was dependent on sialophorin-dependent IL-17A expression but was independent of cell trafficking. Gain of function studies revealed that glycosylated sialophorin enhanced the type 17 responses in dose and duration dependent manner. We also found that glycosylated sialophorin can be used as a functional phenotypic marker to assess vaccine efficacy, disease progression, and clinical outcomes. Our recent studies showed sialophorin promotes the survival of effector type 17 cells and OXPHOS metabolism.
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Speaker
Som Nanjappa obtained a BVSc & AH (DVM) degree from the University of Agricultural Sciences, Bangalore, India. During this period, the passion for research emanated with interest in host responses to pathogens, which led him to secure ‘A Summer Research Fellowship” at the Indian Institute of Sciences (IISc) and Jawaharlal Nehru Center for Advanced Scientific Research (JNCASR) institutions. During Ph.D. program in immunology at the University of Wisconsin-Madison, he worked on immunotherapeutic effects of Interleukin-7 to bolster T cell functions and memory using acute and chronic viral infection models. For his postdoctoral stint, Dr. Nanjappa was invigorated to work on challenging research in fungal immunity, which became one of his hardcore research areas as principal investigator. His passion for research in immunology has endured and expanded to encompass host responses to microbes, pathogens, and cancers. Currently, he is an Associate Professor of Immunology in the Department of Pathobiology at the University of Illinois Urbana-Champaign. His lab research interests include, but are not limited to, innate and adaptive immunity to fungal, bacterial, and parasitic infections in immunocompromised hosts. He is currently funded by an R01 and R03 from NIAID/NIH and a UIUC grant apart from collaborative NIH/DoD grants.