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Hedgehog View to a Kill
Hedgehog (Hh) signaling is best known for its role in development and is a key signaling component of primary cilia. Hh signaling plays a role in T cell development, but whether Hh signaling plays a role in the function of mature effector T cells is unclear. De la Roche et al. (p. 1247; see the Perspective by Le Borgne and Shaw) now show that T cell receptor signaling triggers Hh signaling. When Hh signaling is disrupted, centrosome polarization to the immunological synapse is reduced, and cytotoxic T cell–mediated killing is impaired.
Abstract
The centrosome is essential for cytotoxic T lymphocyte (CTL) function, contacting the plasma membrane and directing cytotoxic granules for secretion at the immunological synapse. Centrosome docking at the plasma membrane also occurs during cilia formation. The primary cilium, formed in nonhematopoietic cells, is essential for vertebrate Hedgehog (Hh) signaling. Lymphocytes do not form primary cilia, but we found and describe here that Hh signaling played an important role in CTL killing. T cell receptor activation, which “prearms” CTLs with cytotoxic granules, also initiated Hh signaling. Hh pathway activation occurred intracellularly and triggered Rac1 synthesis. These events “prearmed” CTLs for action by promoting the actin remodeling required for centrosome polarization and granule release. Thus, Hh signaling plays a role in CTL function, and the immunological synapse may represent a modified cilium.
