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United States Department of Agriculture

Agricultural Research Service

Research Project: MOLECULAR, CELLULAR, AND REGULATORY ASPECTS OF OBESITY DEVELOPMENT IN CHILDREN

Location: Children's Nutrition Research Center

Title: Developmental control of integrin expression regulates Th2 effector homing

Authors
item Lee, Seung-Hyo -
item Prince, Joseph -
item Rais, Muhammad -
item Kheradmand, Farrah -
item Ballantyne, Christie -
item Weitz-Schmidt, Gabriele -
item Smith, C. Wayne -
item Corry, David -

Submitted to: Journal of Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: January 27, 2008
Publication Date: April 1, 2008
Citation: Lee, S., Prince, J.E., Rais, M., Kheradmand, F., Ballantyne, C.M., Weitz-Schmidt, G., Smith, C.W., Corry, D.B. 2008. Developmental control of integrin expression regulates Th2 effector homing. Journal of Immunology. 180(7):4656-4667.

Interpretive Summary: The problem under study in this paper is the mechanism by which a type of white blood cell called a T lymphocyte migrates from the blood into tissues. This is important because these cells are known to play a role in several diseases such as obesity with liver injury, atherosclerosis, and asthma. We show for the first time that specific cell surface molecules are necessary for this process, and this provides a possible approach to developing therapies to control the unnecessary or excessive migration of these cells into tissues during inflammation. Future studies will apply these insights to the inflammatory processes that occur during obesity with associated pathologies such as liver injury and atherosclerosis.

Technical Abstract: Integrin CD18, a component of the LFA-1 complex that also includes CD11a, is essential for Th2, but not Th1, cell homing, but the explanation for this phenomenon remains obscure. In this study, we investigate the mechanism by which Th2 effector responses require the LFA-1 complex. CD11a-deficient T cells showed normal in vitro differentiation and function. However, Th2 cell-dependent allergic lung disease was markedly reduced in CD11a null mice and wild-type mice given LFA-1 inhibitors, whereas control of infection with Leishmania major, a Th1-dependent response, was enhanced. In both disease models, recruitment of IL-4-, but not IFN-gamma-secreting cells, to relevant organs was impaired, as was adhesion of Th2 cells in vitro. These diverse findings were explained by the markedly reduced expression of CD29, an alternate homing integrin, on Th2, but not Th1, cells, which precludes Th2 homing in the absence of CD11a. Thus, murine Th1 and Th2 cells use distinct integrins for homing, suggesting novel opportunities for integrin-based therapeutic intervention in diverse human ailments influenced by Th2 cells.

Last Modified: 8/1/2014