Granzyme A and CD160 expression delineates ILC1 with graded functions in the mouse liver

Chiara Di Censo, Marie Marotel, Irene Mattiola, Lena Müller, Gianluca Scarno, Giuseppe Pietropaolo, Giovanna Peruzzi, Mattia Laffranchi, Julija Mazej, Mohamed Shaad Hasim, Sara Asif, Eleonora Russo, Luana Tomaipitinca, Helena Stabile, Seung Hwan Lee, Laura Vian, Massimo Gadina, Angela Gismondi, Han Yu Shih, Yohei MikamiCristina Capuano, Giovanni Bernardini, Michael Bonelli, Silvano Sozzani, Andreas Diefenbach, Michele Ardolino, Angela Santoni, Giuseppe Sciumè

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

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 GzmACD160+ 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.

Original languageEnglish
JournalEuropean Journal of Immunology
DOIs
Publication statusAccepted/In press - 2021

Keywords

  • CD160
  • granzyme A
  • innate lymphoid cells
  • natural killer
  • Nfil3

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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