| First Author | Shao B | Year | 2020 |
| Journal | J Immunol | Volume | 204 |
| Issue | 1 | Pages | 37-48 |
| PubMed ID | 31757864 | Mgi Jnum | J:294119 |
| Mgi Id | MGI:6451266 | Doi | 10.4049/jimmunol.1900680 |
| Citation | Shao B, et al. (2020) Th1 Cells Rolling on Selectins Trigger DAP12-Dependent Signals That Activate Integrin alphaLbeta2. J Immunol 204(1):37-48 |
| abstractText | During inflammation, both neutrophils and effector T cells use selectins to roll and integrins to arrest in postcapillary venules. In both cell types, chemokines can transduce signals that convert integrin alphaLbeta2 to a high-affinity conformation, which interacts with ICAM-1 to mediate arrest. In neutrophils, selectins also trigger an immunoreceptor-like signaling cascade that converts integrin alphaLbeta2 to an intermediate-affinity conformation, which interacts with ICAM-1 to slow rolling. It is not known whether selectins induce similar signaling events in T cells. Ag engagement causes phosphorylation of ITAMs on the TCR; these motifs recruit kinases and adaptors that lead to the activation of alphaLbeta2. We found that mouse Th1 cells rolling on P- or E-selectin triggered signals that promoted alphaLbeta2-dependent slow rolling on ICAM-1 in vitro and in vivo. The selectin signaling cascade resembled that used by the TCR, except that unexpectedly, Th1 cells employed the ITAM-bearing protein DAP12, which was not known to be expressed in these cells. Importantly, outside-in signaling through ligand-occupied alphaLbeta2 also required DAP12. Cooperative selectin and chemokine signaling in Th1 cells promoted alphaLbeta2-dependent slow rolling and arrest in vitro and in vivo and migration into Ag-challenged tissues in vivo. Our findings reveal an important function for DAP12 in Th1 cells and a new mechanism to recruit effector T cells to sites of inflammation. |
