Abstract

The overall objective of this Program Project is to determine the nature and diversity of mechanism active in the regulation and dysregulation of the immune system in autoimmunities. Such study presupposes that the tools to identify, characterize and manipulate cells, genes and molecules of this system are available to the Program Project. Key tools in this analysis are highly specialized transgenic, mutant, homozygous deficient (""""""""gene knock-out"""""""") congenic, recombinant and other mutant mouse strains. These strains provide the key reagents for each of the projects in this Program Project, and the availability of this type of genetically altered reagents for each of the projects in this Program Project, and the availability of this type of genetically altered animal has in general revolutionized the study of immunobiology. These strains will permit clear study of autoimmunity in vivo and in vitro. Key strains will include TCR+ and Ig- transgenic mice to permit direct analysis of autoreactive T and B cells, and """"""""gene knock-out"""""""" mice to provide genetic backgrounds deficient in specific significant aspects of immunity. These strains are crucial to our studies of autoimmunity. This core mouse breeding facility is thus an essential resource for the research projects.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
2P01AI036529-05
Application #
6099840
Study Section
Project Start
1998-09-30
Project End
1999-08-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
5
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Yale University
Department
Type
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520

  Publications

Doyle, Hester A; Mamula, Mark J (2012) Autoantigenesis: the evolution of protein modifications in autoimmune disease. Curr Opin Immunol 24:112-8
Kamanaka, Masahito; Huber, Samuel; Zenewicz, Lauren A et al. (2011) Memory/effector (CD45RB(lo)) CD4 T cells are controlled directly by IL-10 and cause IL-22-dependent intestinal pathology. J Exp Med 208:1027-40
Choi, Je-Min; Shin, Jae-Hun; Sohn, Myung-Hyun et al. (2010) Cell-permeable Foxp3 protein alleviates autoimmune disease associated with inflammatory bowel disease and allergic airway inflammation. Proc Natl Acad Sci U S A 107:18575-80
Sweet, Rebecca A; Christensen, Sean R; Harris, Michelle L et al. (2010) A new site-directed transgenic rheumatoid factor mouse model demonstrates extrafollicular class switch and plasmablast formation. Autoimmunity 43:607-18
Sanjabi, Shomyseh; Zenewicz, Lauren A; Kamanaka, Masahito et al. (2009) Anti-inflammatory and pro-inflammatory roles of TGF-beta, IL-10, and IL-22 in immunity and autoimmunity. Curr Opin Pharmacol 9:447-53
Herlands, Robin A; Christensen, Sean R; Sweet, Rebecca A et al. (2008) T cell-independent and toll-like receptor-dependent antigen-driven activation of autoreactive B cells. Immunity 29:249-60
Shlomchik, Mark J (2008) Sites and stages of autoreactive B cell activation and regulation. Immunity 28:18-28
Harvey, Bohdan P; Gee, Renelle J; Haberman, Ann M et al. (2007) Antigen presentation and transfer between B cells and macrophages. Eur J Immunol 37:1739-51
Muthukumarana, Poorni; Chae, Wook-Jin; Maher, Stephen et al. (2007) Regulatory transplantation tolerance and ""stemness"": evidence that Foxp3 may play a regulatory role in SOCS-3 gene transcription. Transplantation 84:S6-11
Christensen, Sean R; Shlomchik, Mark J (2007) Regulation of lupus-related autoantibody production and clinical disease by Toll-like receptors. Semin Immunol 19:11-23

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