Type 1 innate lymphoid cells: Soldiers at the front line of immunity

Abstract Innate lymphoid cells (ILCs) are tissue-resident innate lymphocytes that have functions to protect the hosts against pathogens and that regulate tissue inflammation and homeostasis. ILC subsets rapidly produce particular cytokines in response to infection, inflammation, and tissue injury at the local environment. Type 1 ILCs (ILC1s) promptly and abundantly produce interferon (IFN)-γ but lack appreciable cytotoxic activity. ILC1s share many phenotypic, developmental, and functional characteristics with natural killer (NK) cells, which are circulating innate lymphocytes with potent natural cytotoxicity. However, recent studies have established ILC1s as distinct from NK cells. ILC1s predominantly reside in the liver—they initially were discovered as a liver-resident ILC subset—as well as in other lymphoid and non-lymphoid tissues. Accumulating evidence has demonstrated that ILC1s play an important and unique role in host protection and in immunomodulation in their resident organs. However, the pathophysiological role of tissue-resident ILC1s remains largely unclear. In this review, we summarize emerging evidence showing that ILC1s not only contribute to inflammation to protect against pathogens but also promote tissue protection and metabolism. We highlight a unique function of ILC1s in their resident tissues.