Granzyme A and CD160 expression delineates ILC1 with graded functions in the mouse liver. Issue 11 (19th August 2021)

• Record Type: Journal Article
• Authors: Di Censo, Chiara; Marotel, Marie; Mattiola, Irene; Müller, Lena; Scarno, Gianluca; Pietropaolo, Giuseppe; Peruzzi, Giovanna; Laffranchi, Mattia; Mazej, Julija; Hasim, Mohamed Shaad; Asif, Sara; Russo, Eleonora; Tomaipitinca, Luana; Stabile, Helena; Lee, Seung‐Hwan; Vian, Laura; Gadina, Massimo; Gismondi, Angela; Shih, Han‐Yu; Mikami, Yohei; Capuano, Cristina; Bernardini, Giovanni; Bonelli, Michael; Sozzani, Silvano; Diefenbach, Andreas; Ardolino, Michele; Santoni, Angela; Sciumè, Giuseppe
• Is Part Of: European journal of immunology. Volume 51:Issue 11(2021)
• Page Start: 2568
• Page End: 2575
• Publication Date: 2021-08-19
• Subjects: CD160 -- granzyme A -- innate lymphoid cells -- natural killer -- Nfil3; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.202149209
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract: Type 1 innate lymphoid cells (ILC1) are tissue‐resident lymphocytes that provide early protection against bacterial and viral infections. Discrete transcriptional states of ILC1 have been identified in homeostatic and pathological contexts. However, whether these states delineate ILC1 with different functional properties is not completely understood. Here, we show that liver ILC1 are heterogeneous for the expression of distinct effector molecules and surface receptors, including granzyme A (GzmA) and CD160, in mice. ILC1 expressing high levels of GzmA are enriched in the liver of adult mice, and represent the main hepatic ILC1 population at birth. However, the heterogeneity of GzmA and CD160 expression in hepatic ILC1 begins perinatally and increases with age. GzmA + ILC1 differ from NK cells for the limited homeostatic requirements of JAK/STAT signals and the transcription factor Nfil3 . Moreover, by employing Rorc(γt) ‐fate map (fm) reporter mice, we established that ILC3‐ILC1 plasticity contributes to delineate the heterogeneity of liver ILC1, with RORγt‐fm + cells skewed toward a GzmA – CD160 + phenotype. Finally, we showed that ILC1 defined by the expression of GzmA and CD160 are characterized by graded cytotoxic potential and ability to produce IFN‐γ. In conclusion, our findings help deconvoluting ILC1 heterogeneity and provide evidence for functional diversification of liver ILC1. Abstract : Di Censo et al. identified distinct ILC1 populations in the mouse liver, defined by the expression of granzyme A (GzmA) and CD160. Expression of these molecules is finely tuned perinatally and delineates ILC1 with graded ability to produce IFN‐γ and to kill cancer cells. Moreover, ILC3‐ILC1 plasticity contributes to determining the heterogeneity of liver ILC1. These findings help deconvoluting phenotypic and functional heterogeneity of liver ILC1.