期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 44, 期 12, 页码 3484-3499出版社
WILEY
DOI: 10.1002/eji.201344428
关键词
Adaptor protein; LFA-1; Outside-in signaling; T-cell migration
类别
资金
- Higher Education Authority (HEA) of Ireland
- Ministry of Education (MOE)-Nanyang Technological University (NTU) Singapore [L0412130.010, L0412290.010]
The integrin lymphocyte function associated antigen-1 (LFA-1) plays a key role in leukocyte trafficking and in adaptive immune responses through interactions with adhesive ligands, such as ICAM-1. Specific blockade of these interactions has validated LFA-1 as a therapeutic target in many chronic inflammatory diseases, however LFA-1 antagonists have not been clinically successful due to the development of a general immunosuppression, causing fatal side effects. Growing evidence has now established that LFA-1 mediates an array of intracellular signaling pathways by triggering a number of downstream molecules. In this context, a class of multimodular domain-containing proteins capable of recruiting two or more effector molecules, collectively known as adaptor proteins, has emerged as important mediators in LFA-1 signal transduction. Here, we provide an overview of the adaptor proteins involved in the intracellular signaling cascades by which LFA-1 regulates T-cell motility and immune responses. The complexity of the LFA-1-associated signaling delineated in this review suggests that it may be an important and challenging focus for future research, enabling the identification of tunable targets for the development of immunotherapies.
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