AI Article Synopsis
- Tec family kinases are crucial for macrophage survival through M-CSF-induced signaling, as their absence leads to increased cell death and reduced macrophage numbers.
- In macrophages lacking Tec or Btk, there is an elevation in caspase-11 activation, indicating a link to cell death pathways.
- The study also reveals that Tec and Btk are necessary for the correct expression of the GM-CSF receptor alpha chain in macrophages, highlighting their role in lineage-specific signaling regulation.
Article Abstract
Tec family kinases have important roles in lymphocytes; however, little is known about their function in monocytes/macrophages. In this study we report that Tec family kinases are essential for M-CSF (M-CSF)-induced signaling pathways that regulate macrophage survival. Compared with wild-type bone marrow-derived macrophage (BMM) cultures, Tec(-/-)Btk(-/-) BMM cultures displayed increased cell death that correlated with a severe drop in macrophage numbers. In addition, macrophages deficient in either Tec or Btk showed expression and activation of caspase-11. Elucidation of M-CSF receptor (M-CSFR) signaling pathways revealed that the total tyrosine phosphorylation pattern upon M-CSF stimulation was altered in Tec(-/-)Btk(-/-) macrophages despite normal expression and phosphorylation of the M-CSFR. Further, Tec and Btk are required for proper expression of the GM-CSF receptor alpha (GM-CSFRalpha) chain in macrophages but not dendritic cells, implicating Tec family kinases in the lineage-specific regulation of GM-CSFRalpha expression. Taken together, our study shows that Tec and Btk regulate M-CSFR signaling-induced macrophage survival and provides a novel link between Tec family kinases and the regulation of caspase-11 and GM-CSFRalpha expression.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3001193 | PMC |
| http://dx.doi.org/10.4049/jimmunol.180.12.8048 | DOI Listing |
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