Immunobiology of the skin-specific receptor CLEC2A/KACL

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Natural Killer (NK) cells are lymphocytes of the innate immune system and were originally described due to their capacity to kill virus-infected or malignant 'self' cells. Subsequently, additional functions of NK cells became apparent such as secretion of cytokines, modulation of immune responses, and regulation of tissue homeostasis. Recently, additional types of innate lymphocytes were described that are rare in the peripheral blood, are characterized by a peculiar cytokine pattern and thought to be involved in tissue homeostasis. Reactivity of these innate lymphocytes is determined by cell surface receptors upon interaction with cognate ligands. Here, we propose to continue our studies on a novel and unique receptor/ligand pair where the receptor (NKp65) is expressed on a rare subset of innate lymphocytes, while expression of the ligand (KACL) is restricted to human keratinocytes as shown by our previous work. Here we plan to characterise NKp65-expressing lymphocytes in terms of phenotype and function, to address regulation of NKp65 expression, and to study functional consequences of NKp65/KACL interaction. From these studies, we do expect novel and significant insights into the biology and tissue-specific function of innate lymphocytes as well as into the immunobiology of human skin.