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PMID:23526587
| Citation |
Pérez-Rivero, G, Cascio, G, Soriano, SF, Sanz, AG, de Guinoa, JS, Rodríguez-Frade, JM, Gomariz, RP, Holgado, BL, Cabañas, C, Carrasco, YR, Stein, JV and Mellado, M' (2013) Janus kinases 1 and 2 regulate chemokine-mediated integrin activation and naïve T-cell homing. Eur. J. Immunol. ' |
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| 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, non-activated 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 ERM (ezrin/radixin/moesin) dephosphorylation and F-actin polymerization, as well as activation of lymphocyte function-associated antigen-1 and very late antigen-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. |
| Links |
PubMed Online version:10.1002/eji.201243178 |
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Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0019221: cytokine-mediated signaling pathway |
ECO:0000314: |
P |
JAK2 is essential to naive t cell homing. Figure 2C demonstrates that silencing JAK1/2 proteins severely inhibited the ability of chemokine-mediated t cell signaling. This indicated by the naive t-cell's inability to migrate through a chemokine gradient. |
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See also
References
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