Immunology Graduate Group

David Artis, Ph.D.
Assistant Professor, Pathobiology

Address:
University of Pennsylvania
School of Veterinary Medicine
314 Hill Pavillion
380 South University Avenue, Philadelphia. PA. 19104-4539. USA
Office Phone: 215.898.7920
Lab Phone: 215.898.6268
Fax: 215.746.2295
Email:  dartis@vet.upenn.edu

Websites:
Department of Pathobiology
CAMB Graduate Group, Microbiology, Virology and Parasitology Program (MVP)
http://www.med.upenn.edu/camb/faculty/mv/artis.html

http://www.med.upenn.edu/micro/faculty/artis.html

Education:
Ph.D., University of Manchester, UK
BSc (Hons), University of Glasgow, UK

Research Interests

Regulation of immunity and inflammation in the gastrointestinal tract

Research Summary  

The goals of the lab are to gain a better understanding of the immuno-regulatory mechanisms that govern the initiation, regulation, and development of immune effector responses following infection with pathogens of the gastrointestinal tract. The gut is a unique immunologic niche, simultaneously maintaining tolerance to food antigens and billions of enteric bacterial symbionts, while retaining the ability to recognize and respond to potentially dangerous pathogens.

We are particularly interested in gut-dwelling helminth parasites. An estimated two billion people world-wide are infected with soil transmitted helminth parasites, with 300 million people suffering severe infections. In addition, this group of pathogens represents a significant economic burden to the livestock industry. Despite their ubiquitous distribution and evolutionary success, many of the pathogen factors that promote parasitism and the host factors that mediate resistance to these infections remain poorly defined.

Trichuris muris is one of the model systems we use to investigate the cellular and molecular mechanisms that govern immunity and inflammation following infection. T. muris is a natural gastrointestinal parasite of mice and provides an immunologically well-defined model of human and veterinary infections. Previous studies have shown that CD4 + T helper type 1 (Th1) responses promote chronic infection, while CD4 + Th2 responses are required for host protective immunity. However, the cellular and molecular mechanisms that control how Trichuris is recognized by the innate immune system, how CD4 + T helper cell differentiation is regulated in the gut, and what the immune effector mechanisms are that mediate expulsion of these infections are unknown.

There are four key research areas in the lab:

1. How do intestinal epithelial cells (iEC) and intestinal dendritic cells (iDC) regulate innate responses to Trichuris and other enteric pathogens? Using a combination of cell lineage-specific knockout mice and adoptive transfers of highly purified antigen presenting cell populations, we are defining how innate responses against enteric pathogens such as Trichuris and other gut pathogens are initiated.
2. What unique regulatory pathways control CD4 + T helper cell differentiation and the development of T cell memory following infection in the gastrointestinal tract? Many factors are known to influence CD4 + T helper cell fate in lymphoid tissues, including the type of antigen presenting cell, costimulatory molecules, and the cytokine environment. Using new tools, we are defining how pathogen-specific CD4 + T cell responses develop and are maintained in the gut microenvironment.
3. What are the immune effector mechanisms elicited by CD4 + Th2 cells that mediate host protective immunity in the gut? The effector mechanisms that mediate expulsion of GI helminth parasites remain unknown. Using a combination of global gene profiling and proteomic analysis we have identified a number of novel gut-specific immune effector molecules against parasites and are now testing their functions and potential for development as anti-microbial agents.
4. How have helminth parasites evolved to subvert the mammalian immune defenses? Helminth parasites have evolved elaborate physical, biochemical, and molecular adaptations to promote their survival. We are defining molecular mechanisms that helminth parasites utilize to inhibit inflammation and protective immune responses in the gut microenvironment. Understanding these pathways will be useful in the design of therapeutics to target helminth infection and other pathologies associated with chronic intestinal inflammation.

Recent Publications

1. Tu, L, Fang, TC, Artis, D*, Shestova, O, Pross, S, Maillard, I, and Pear, WS (2005) Notch signaling is essential to generate type 2 immunity in vivo. Journal of Experimental Medicine 202: 1037-1042. *Joint first author.
2. Hutchens, A, Artis, D, Bird, AP, Scott, P, and Reiner, SL (2005) A critical role for gene silencing in organizing T helper cell-mediated immunity. Journal of Immunology 175:5606-5610.
3. Tilney, LG, Connelly, PS, Guild, GM, Vranich, KA, and Artis, D (2005) Adaptation of a nematode parasite to living within the mammalian epithelium. Journal of Experimental Zoology 303A: 927-945.
4. Tato, CM, Mason, N, Artis, D, Shapira, S, Caamano, JC,  Bream, JH, Liou, HC, Hunter, CA (2006) Opposing roles of NF-B family members in the regulation of NK cell proliferation and production of IFN-g. International Immunology 18:505-513.
5. Hogan, S. P., Seidu, L., Blanchard, C., Groschwitz, K., Mishra, A., Karow, M. L., Ahrens, R., Artis, D., Murphy, A. J., Valenzuela, D. M., Yancopoulos, G. D., Rothenberg, M. E. (2006) Resistin-like molecule beta regulates innate colonic function: barrier integrity and inflammation susceptibility J Allergy Clin Immunol. 118:257-268.
6. Wilson EH, Zaph C, Mohrs M, Welcher A, Siu J, Artis D, Hunter CA. (2006) B7RP-1-ICOS interactions are required for optimal infection-induced expansion of CD4+ Th1 and Th2 responses. Journal of Immunology 177:2365-72.
7. Zaph, CJ, Rook, K, Mohrs, M, Scott, P, and Artis, D (2006) Persistence, function, and lineage-relationship of effector and central memory CD4+ T cells following infection with a gastrointestinal pathogen. Journal of Immunology 177:511-518.
8. Owyang, A, Zaph, CJ, Wilson, E, Guild, K, McClanachan, T, Miller, HRP, Cua, D, Goldschmidt, M, Hunter, C, Kastelein, R, and Artis, D (2006) IL-25 is a critical regulator of immunity and inflammation in the gastrointestinal tract. Journal of Experimental Medicine 203:843-849.
9. Perrigoue, JG, Li, J, Zaph, C, Goldschmidt, M, Scott, P, Pearce, EJ, Ghilardi, N, Artis, D (2007). IL-31-IL-31R interactions negatively regulate type 2 inflammation in the lung. Journal of Experimental Medicine 204:481-487.
10. Zaph, C, Troy, AE, Taylor, BC, Berman-Booty, LD, Guild, KJ, Du, Y, Yost, E, Gruber, A, May, MJ, Greten, F, Eckmann, L, Karin, K, and Artis, D. (2007). Epithelial cell-intrinsic IKKb expression regulates intestinal immune homeostasis. Nature 446:552-556.

 

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