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Molecular Immunology

Significant Accomplishments

Advances in Defining Merocytic Dendritic Cells

The research program of Edith Janssen, PhD, aims at molecular analysis and translational exploitation of immune responses to self. Janssen has made major strides in defining the unique capabilities, and likely therapeutic utility, of a novel dendritic cell population that she discovered, merocytic dendritic cells. Merocytic dendritic cells orchestrate effector immune responses to self. Harnessing these dendritic cells significantly increases the efficacy of anti-tumor vaccines in mice (J. Immunol, 185:3337; Clin Exp Immunol, 163:381). On the other hand, merocytic dendritic cells can play an important pathogenic role in autoimmune disease − breaking T-cell tolerance to beta cell antigens and driving type 1 diabetes in mice (J Immunol, 185:1999; work done in collaboration with Jonathan Katz, PhD).

Understanding Regulatory T Cells

Homeostasis and avoidance of immune-mediated pathology demands tight regulation of the amplitude, duration and class immune responses − something provided by numerous, often overlapping mechanisms of immune counter-regulation. The research program of Claire Chougnet, PhD, DPharm, on regulatory T cells, a subset of immune cells with important counter-regulatory roles across the immune system, continues to bear important fruit. Work published in the last year has demonstrated that: (a) regulatory T cells act in a contact-dependent manner to restrain HIV replication in activated T cells − something that may be of particular relevance to the course of early HIV infection (Blood, 117:5372); (b) the pro-apoptotic molecule, Bim, plays a major role in regulatory T-cell homeostasis (J Immunol, 186:156; work done in collaboration with David Hildeman, PhD); and (c) chorioamnionitis, which leads to ileal inflammation that interferes with gut maturation, is associated with depletion of intestinal regulatory T cells in sheep models (PLoS One, 6:e18355; work done in collaboration with Suhas Kallapur, MD, Alan Jobe, MD, PhD, and investigators from Maastricht University Medical Center).

Seeking a More Humanized Mouse Model

Mice have triumphed as the in vivo experimental model system of choice in biomedical research. However, there are clear limitations to mouse models. The literature is full of therapeutic approaches that worked in mice but failed in humans. Further, mice often provide poor mimics of the human diseases being modeled. Christopher Karp, MD, is addressing the novel hypothesis that the cold stress that laboratory mice are ubiquitously subjected to (a practical “paradigm” employed systematically for nonscientific reasons − the comfort of their clothed human handlers) profoundly affects mouse pathophysiology in ways that directly impair modeling of human immunology and immune-mediated disease. The goal of this research program is the rapid development of better, more humanized models of immunity and immune-mediated disease.