Janus kinases 1 and 2 regulate chemokine-mediated integrin activation and naïve T-cell homing.
Publisher DOI
PubMed ID
23526587
Abstract
Janus kinases (JAKs) are central signaling molecules in cytokine receptor cascades. Although they have also been implicated in chemokine receptor signaling, this function continues to be debated. To address this issue, we established a nucleofection model in primary, nonactivated mouse T lymphocytes to silence JAK expression and to evaluate the ability of these cells to home to lymph nodes. Reduced JAK1 and JAK2 expression impaired naïve T-cell migration in response to gradients of the chemokines CXCL12 and CCL21. In vivo homing of JAK1/JAK2-deficient cells to lymph nodes decreased, whereas intranodal localization and motility were unaffected. JAK1 and JAK2 defects altered CXCL12- and CCL21-triggered ezrin/radixin/moesin (ERM) dephosphorylation and F-actin polymerization, as well as activation of lymphocyte function-associated Ag-1 and very late Ag-4 integrins. As a result, the cells did not adhere firmly to integrin substrates in response to these chemokines. The results demonstrate that JAK1/JAK2 participate in chemokine-induced integrin activation and might be considered a target for modulation of immune cell extravasation and therefore, control of inflammatory reactions.
Date Issued
2013-07
Publication Type
Article
Subject(s)
Subjects
Chemokine receptor
•
Integrin
•
Janus kinase
•
Lymphocyte homing
Language(s)
en
Author(s)
Pérez-Rivero, Gema | |
Cascio, Graciela | |
Soriano, Silvia Fernández | |
Sanz, Álvaro Gil | |
de Guinoa, Julia Sáez | |
Rodríguez-Frade, José Miguel | |
Gomariz, Rosa P. | |
Holgado, Borja L. | |
Cabañas, Carlos | |
Carrasco, Yolanda R. | |
Mellado, Mario |
Additional Credits
Journal
European journal of immunology
Publisher
Wiley-VCH
ISSN
0014-2980
Access(Rights)
restricted