Recent advances on T-cell regulation by receptor tyrosine... : Current Opinion in Hematology (original) (raw)
Lymphoid biology and diseases
Laboratory of Immunology and aNephrology Service of Notre Dame Hospital, Centre Hospitalier de l'Université de Montréal, Montreal, Canada
This study was supported by grants from the Canadian Institutes of Health Research (CIHR, MOP57697 and MOP69089), the Kidney Foundation of Canada, the Heart and Stroke Foundation of Quebec, the Roche Organ Transplantation Research Foundation, Switzerland (ROTRF #590934439), the Juvenile Diabetes Research Foundation, USA (1-2005-197), Genome Canada/Genome Quebec, and the J-Louis Levesque Foundation to J W. This work is also supported by a group grant from the CIHR for New Emerging Teams in Transplantation. J W is a National Scholar of the Fonds de la Recherche en Santé du Québec.
Correspondence to Dr Jiangping Wu, Laboratory of Immunology, Research Centre, CHUM, Notre Dame Hospital, Pavilion DeSève, Room Y-5616, 1560 Sherbrooke Street East, Montreal, Quebec H2L 4M1, Canada
Tel: 514 890 8000 ext. 25164; fax: 514 412 7596; e-mail: [email protected]
Abstract
Purpose of review
This review summarizes recent knowledge on the role of receptor tyrosine kinases, particularly erythropoietin-producing hepatocyte kinases (Ephs), in T-cell function and development.
Recent findings
Erythropoietin-producing hepatocyte kinase function and signaling in the immune system have been recently investigated. Cross-linking some Ephs results in T-cell costimulation and reduces the response threshold of T-cell receptor activation. In vivo, T-cell-mediated responses are compromised in EphB6−/− mice. Some Ephs are shown to control T-cell migration and adhesion, as well as the integrity of lymphoid organ structure.
Summary
Ephs are the largest family of receptor tyrosine kinases. Some Ephs are expressed in the lymphoid organs. Ephrins, ligands of Ephs, are also cell surface molecules. Cross-linking of certain Ephs facilitates T-cell activation and proliferation. Under physiologic conditions, such cross-linking by ephrins likely occurs in lymphoid organs, where ephrins on T cells interact with ephrins on the surface of neighboring fraternal T cells or antigen-presenting cells; this may explain why T-cell responses are more effectively initiated in the lymphoid organs. Certain Ephs are also critical for lymphocyte adhesion and migration and for proper lymphoid organ structure. Ephs and ephrins are highly redundant and their interactions promiscuous, suggesting pivotal roles of these molecules in biology. Conversely, such redundancy represents a major challenge to further dissection of the function of individual Ephs. Multiple tissue-specific gene null mutations on Ephs or ephrins will likely reveal more interesting immune-related phenotypes.
© 2005 Lippincott Williams & Wilkins, Inc.