Abstract

This is a new application that proposes to study regulation of chemokine receptor expression by cytokines in experimental granulomas, and to evaluate the contributions of these various receptors to the granulomatous response. The PI previously developed a novel murine model of synchronized T cell-mediated granuloma formation using agarose beads coated with either mycobacterial or schistosomal antigens to elicit the formation of lesions that show type 1 or type 2 cytokine responses, respectively. These studies demonstrated that cytokine and chemokine receptor expression differ in the two distinct granulomata. The experiments proposed here will extend previous studies which examined the contribution of selected cytokines to the development of granulomas in vivo.
In Aim 1, flow cytometry and RT-PCR will be used to define the profiles of chemokine receptor expression in leukocyte populations during the course of granuloma development.
Aim 2 will characterize granuloma formation in chemokine receptor knockout mice.
Aim 3 will attempt to determine the roles of selected cytokines in regulating chemokine receptor expression during granuloma formation, using cytokine knockout mice or anti-cytokine antibodies. Lastly, in Aim 4, the PI will attempt to manipulate granuloma formation in vivo by administering chemokines, and truncated chemokines that function as receptor antagonists, via osmotic pumps.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI043460-04
Application #
6373888
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Voulgaropoulou, Frosso
Project Start
1998-08-01
Project End
2002-07-31
Budget Start
2001-08-01
Budget End
2002-07-31
Support Year
4
Fiscal Year
2001
Total Cost
$145,026
Indirect Cost

  Institution

Name
University of Michigan Ann Arbor
Department
Pathology
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109

  Publications

Chiu, Bo-Chin; Martin, Brian E; Stolberg, Valerie R et al. (2013) The host environment is responsible for aging-related functional NK cell deficiency. J Immunol 191:4688-98
Chensue, Stephen W (2013) Chemokines in innate and adaptive granuloma formation. Front Immunol 4:43
Chiu, Bo-Chin; Martin, Brian E; Stolberg, Valerie R et al. (2013) Cutting edge: Central memory CD8 T cells in aged mice are virtual memory cells. J Immunol 191:5793-6
Stolberg, Valerie R; Chiu, Bo-chin; Martin, Brian E et al. (2011) Cysteine-cysteinyl chemokine receptor 6 mediates invariant natural killer T cell airway recruitment and innate stage resistance during mycobacterial infection. J Innate Immun 3:99-108
Stolberg, Valerie R; Chiu, Bo-Chin; Schmidt, Brian M et al. (2011) CC chemokine receptor 4 contributes to innate NK and chronic stage T helper cell recall responses during Mycobacterium bovis infection. Am J Pathol 178:233-44
Schaller, Matthew A; Logue, Hannah; Mukherjee, Sumanta et al. (2010) Delta-like 4 differentially regulates murine CD4 T cell expansion via BMI1. PLoS One 5:e12172
Hu, Jerry S; Freeman, Christine M; Stolberg, Valerie R et al. (2006) AMD3465, a novel CXCR4 receptor antagonist, abrogates schistosomal antigen-elicited (type-2) pulmonary granuloma formation. Am J Pathol 169:424-32
Freeman, Christine M; Stolberg, Valerie R; Chiu, Bo-Chin et al. (2006) CCR4 participation in Th type 1 (mycobacterial) and Th type 2 (schistosomal) anamnestic pulmonary granulomatous responses. J Immunol 177:4149-58
Freeman, Christine M; Chiu, Bo-Chin; Stolberg, Valerie R et al. (2005) CCR8 is expressed by antigen-elicited, IL-10-producing CD4+CD25+ T cells, which regulate Th2-mediated granuloma formation in mice. J Immunol 174:1962-70
Chiu, Bo-Chin; Freeman, Christine M; Stolberg, Valerie R et al. (2004) Impaired lung dendritic cell activation in CCR2 knockout mice. Am J Pathol 165:1199-209

Showing the most recent 10 out of 16 publications