IL-7 activates alpha4beta1 integrin in murine thymocytes.
IL-7, a cytokine produced by thymic epithelium, was shown to induce adhesion of murine thymocytes to gelatin-coated membranes. A major binding component of gelatin was identified as fibronectin. IL-7-induced adhesion was observed for all of the major thymocyte subsets, including double-negative, double-positive, and single-positive cells, and specific IL-7R were verified on each subset. Fibronectin binding was mediated via alpha4beta1 integrin (VLA-4), which is expressed at high levels on thymocytes. VLA-4 surface expression was not increased following IL-7 treatment, but was shown to undergo rapid tyrosine phosphorylation on the beta1 subunit. This tyrosine phosphorylation was blocked by genistein, which also blocked IL-7-induced adhesion. IL-7 was detected on the extracellular matrix of the thymus, suggesting that it could promote matrix association through an integrin pathway.
Kitazawa
H
H
Laboratory of Immunoregulation, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.
Muegge
K
K
Badolato
R
R
Wang
J M
JM
Fogler
W E
WE
Ferris
D K
DK
Lee
C K
CK
Candéias
S
S
Smith
M R
MR
Oppenheim
J J
JJ
Durum
S K
SK
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D019833:Genistein; D039041:Integrin alpha4beta1; D016023:Integrins / Q000187:drug effects* / Q000502:physiology; D015851:Interleukin-7 / Q000494:pharmacology*; D007529:Isoflavones / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D016201:Receptors, Lymphocyte Homing / Q000187:drug effects* / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism
D004791:Enzyme Inhibitors; D005353:Fibronectins; D039041:Integrin alpha4beta1; D016023:Integrins; D015851:Interleukin-7; D007529:Isoflavones; D016201:Receptors, Lymphocyte Homing; D019833:Genistein