Text Image: UM Medical School: Graduate Program in Immunology
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Chensue

Stephen W. Chensue, M.D., Ph.D.
Professor of Pathology

Chief, Pathology and Laboratory Medicine
Veteran Affairs

schensue@umich.edu

Numerous diseases involve aberrant immune and inflammatory responses. The primary focus of my laboratory studies is to determine the in vivo function of the molecular signals, cytokines and chemokines that mediate inflammation and immunity. We have developed standardized mouse models of pulmonary hypersensitivity-type granulomatous inflammation induced by antigens of Mycobacteria sp. and Schistosoma mansoni in order to analyze the dynamics of Th1 and Th2-mediated hypersensitivity responses. This involves examination of both innate and adaptive components of the responses with regard to T cell and dendritic cell biology.

We monitor a wide variety of cytokines including interleukins, interferons, colony stimulation factors, tumor necrosis factors and chemokines. To this end, we use a number of immunoassays and bioassays to detect the presence of cytokines and chemokines during various stages of the inflammation.

In addition, selective depletion or receptor blockade studies are used to determine the extent and nature of mediator participation in innate and adaptive immune events. After various targeted manipulations, intact lesions or their cellular components are sequentially isolated and examined. Responses are also examined using transgenic mice as well as mice with specific knockout of cytokine genes or genes for cytokine/chemokine receptors. Other technologies employed include real-time polymerase chain reactions (RT-PCR) to detect cytokine mRNA, laser capture microdissection, in vivo plasmid-mediated gene transduction, in vitro chemotactic assays and flow cytometry.

Thus far, our work has revealed diverse but carefully orchestrated patterns of mediator production including those dictate the inflammatory response and interact with other physiologic systems. We have shown that inflammatory reactions can be classified upon the basis of the spectrum of cytokines involved. Moreover, these reactions can be modulated by cytokine and chemokine targeted manipulations. Webpage at www.pathology.med.umich.edu/chensuelab/index.htm

Representative Publications

  1. Chiu, B., Freeman, C.M., Stolberg , V.R., Hu J.S., Zeibecoglou, K., Lu, B., Gerard, C., Charo, I.F., Lira, S. A. and Chensue, S.W. Impaired lung dendritic cell activation in CCR2 knockout mice. Am. J. Pathol. 2004, 165:1199-1209.

  2. Freeman, C.M, Chiu, B., Stolberg, V.R., Hu, J., Zeibecoglou, K., Lukacs, N.K., Lira, S.A., Kunkel, S. L., and Chensue, S.W. CCR8 is expressed by antigen-elicited, IL-10 producing CD4+CD25+ T cells which regulate Th2-mediated granuloma formation in mice. J. Immunol. 2005, 174:1962-1970.

  3. Stolberg , V.R., Chiu, B., Komuniecki, E., Freeman, C.M., and Chensue, S.W. Analysis of inducible costimulatory (ICOS) molecule participation during the induction and elicitation of granulomatous responses to mycobacterial and schistosomal antigens. Cell. Immunol. 2005, 237: 45-54.

  4. Chensue, S.W. CXCL-1 (GRO-1)-CXCL3 (GRO3). In, Encyclopedia of Respiratory Medicine, G. Laurent, S. Shapiro, eds., Elsevier Limited: Oxford , UK , pp. 407-410. 2006.

  5. Hu, J.S., Freeman, C.M, Stolberg, V.R., Chiu, B.C., Bridger, G. J., Fricker, S.P., Lukacs, N.W. and Chensue, S.W. AMD3465, a Novel CXCR4 Receptor Antagonist, Abrogates Schistosomal Antigen-elicited (Type-2) Pulmonary Granuloma Formation. Am. J. Pathol. 2006, Aug;169(2):424-32.

  6. Freeman, C.M, Stolberg , V.R., Chiu, B., Lukacs, N.K., Kunkel, S. L., and Chensue, S.W. CC chemokine receptor 4 (CCR4) participation in Th1 (Mycobacterial) and Th2 (Schistosomal) anamnestic pulmonary granulomatous responses J. Immunol. 2006, Sep 15;177(6):4149-58.

  7. Furtado GC, Pina B, Tacke F, Gaupp S, van Rooijen N, Moran TM, Randolph GJ, Ransohoff RM, Chensue SW, Raine CS, Lira SA. A novel model of demyelinating encephalomyelitis induced by monocytes and dendritic cells. J Immunol . 2006 Nov 15;177(10):6871-9.

  8. Chiu BC, Stolberg VR, Freeman CM, Chensue SW. Mononuclear phagocyte-derived interleukin-10 suppresses the innate pulmonary granuloma cytokine response in aged mice. Am J Pathol. 2007 Sep;171(3):829-37.

  9. Freeman CM, Curtis JL, Chensue SW. CC chemokine receptor 5 and CXC chemokine receptor 6 expression by lung CD8+ cells correlates with chronic obstructive pulmonary disease severity. Am J Pathol. 2007 Sep;171(3):767-76.

  10. Choi SW, Hildebrandt GC, Olkiewicz KM, Hanauer DA, Chaudhary MN, Silva IA, Rogers CE, Deurloo D, Fisher JM, Liu C, Adams D, Chensue SW, Cooke KR. CCR1:CCL5 (RANTES) receptor ligand interactions modulates allogeneic T cell responses and reduces graft-versus-host disease following stem cell transplantation. Blood. 2007 Jul 19.

  11. Ito T, Schaller M, Hogaboam CM, Standiford TJ, Chensue SW, Kunkel SL. TLR9 activation is a key event for the maintenance of a mycobacterial antigen-elicited pulmonary granulomatous response. Eur J Immunol . 2007 Oct;37(10):2847-55.



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