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Jakob von Moltke, Ph.D.

E-545 Box 358059 | 750 Republican Street Seattle, WA 98109
(206) 685-8893

Lab Staff

James Jaffe - Research Scientist
Jakob von Moltke, Ph.D.
Assistant Professor, University of Washington School of Medicine - Department of Immunology

The Moltke lab studies immune responses to parasitic worms (helminths) and allergens. These responses, collectively known as type 2 immunity, are triggered by an astonishing diversity of agonists, from macroscopic live worms to microscopic inert particles to soluble enzymes. How do these all look the same to the mammalian immune system? To answer this question, we focus on the initiation of type 2 immunity, when the immune system first encounters a disturbance and must decide how to respond. Using laboratory mice and the helminths Nippostrongylus brasiliensis and Heligmosomoides polygyrus as model organisms, our goal is to provide insights that will lead to improved treatment and prevention of asthma, allergy, and other type 2 inflammatory conditions.

Among the first cells activated during a type 2 response are the group 2 innate lymphoid cells (ILC2s). ILC2s serve as the predominant early source of the cytokines that together give rise to many of the hallmarks of type 2 immunity, such as eosinophilia, increased mucus production, hypercontractility of smooth muscle, and tissue remodeling. Importantly, ILC2s cannot directly sense the presence of type 2 agonists (worms, allergens, etc.) and are instead activated by signals from their surrounding tissue. The identity, source, and regulation of these ILC2-activating signals are the current focus of projects in the lab.

We are particularly interested in specialized epithelial cells called tuft cells. Although they were discovered more than 50 years ago, the function of tuft cells remained unclear. Recently, we and others demonstrated that tuft cells are the exclusive source of the ILC2-activating cytokine IL-25 in the intestine. During worm infection, a feed forward loop comprised of tuft cells, ILC2s, and the epithelial stem cell compartment leads to dramatic epithelial remodeling, and without tuft cell-derived IL-25, worm clearance is delayed. We are currently investigating how else tuft cells contribute to the type 2 immune response. 

University of Washington