Dataset Information

Th1 Cells Rolling on Selectins Trigger DAP12-Dependent Signals That Activate Integrin ?L?2.

ABSTRACT: 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 ?L?2 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 ?L?2 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 ?L?2. We found that mouse Th1 cells rolling on P- or E-selectin triggered signals that promoted ?L?2-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 ?L?2 also required DAP12. Cooperative selectin and chemokine signaling in Th1 cells promoted ?L?2-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.

SUBMITTER: Shao B

PROVIDER: S-EPMC6920551 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Th1 Cells Rolling on Selectins Trigger DAP12-Dependent Signals That Activate Integrin αLβ2.

Shao Bojing B Yago Tadayuki T Panicker Sumith R SR Zhang Nan N Liu Zhenghui Z McEver Rodger P RP

Journal of immunology (Baltimore, Md. : 1950) 20191122 1

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 αLβ2 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 αLβ2 to an intermediate-affinity conformation, which interacts with ICAM-1 to slow rolling. It is not know ...[more]

PMID: 31757864

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Dataset Information

Th1 Cells Rolling on Selectins Trigger DAP12-Dependent Signals That Activate Integrin ?L?2.

Publications

Th1 Cells Rolling on Selectins Trigger DAP12-Dependent Signals That Activate Integrin αLβ2.

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