Deciphering the syntax of cytotoxic lymphocyte degranulation.

In the killer lymphocyte, the targeted delivery of perforin- and granzyme-containing cytotoxic granules to the immunological synapse is crucial for the eradication of pathogen-infected or transformed targets. This process is achieved through a tightly controlled and highly efficient granule exocytosis pathway. Mutations in the granule trafficking proteins Munc13-4, syntaxin 11, Munc18-2 or Rab27 leads to a fatal lapse of immune surveillance and can be manifested as haemophagocytic lymphohistiocytosis in humans. Elucidation of the role of these proteins in exocytic trafficking is pivotal for our understanding of their role in health and disease. In this issue of the European Journal of Immunology, D'Orlando et al. [Eur. J. Immunol. 2013. 43: 194-208] make an important step in this direction, as they generate and characterise syntaxin 11 deficient mice. Herein, we discuss the role of syntaxin-11 in soluble NSF (N-ethylmaleimide sensitive fusion) attachment protein receptors complex formation leading to cytotoxic lymphocyte degranulation and its importance in maintaining immune homeostasis.