Deconstructing iNKT cell development at single-cell resolution

Thomas Baranek; Carolina de Amat Herbozo; Thierry Mallevaey; Christophe Paget

doi:10.1016/j.it.2022.04.012

Deconstructing iNKT cell development at single-cell resolution

Trends Immunol. 2022 Jul;43(7):503-512. doi: 10.1016/j.it.2022.04.012. Epub 2022 May 31.

Authors

Thomas Baranek¹, Carolina de Amat Herbozo², Thierry Mallevaey³, Christophe Paget⁴

Affiliations

¹ Centre d'Étude des Pathologies Respiratoires (CEPR), Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche 1100, Faculté de Médecine, Université de Tours, Tours, France.
² Department of Immunology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
³ Department of Immunology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada. Electronic address: thierry.mallevaey@utoronto.ca.
⁴ Centre d'Étude des Pathologies Respiratoires (CEPR), Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche 1100, Faculté de Médecine, Université de Tours, Tours, France. Electronic address: christophe.paget@inserm.fr.

PMID: 35654639
DOI: 10.1016/j.it.2022.04.012

Abstract

Invariant natural killer T (iNKT) cells are increasingly regarded as disease biomarkers and immunotherapeutic targets. However, a greater understanding of their biology is necessary to effectively target these cells in the clinic. The discovery of iNKT1/2/17 cell effector subsets was a milestone in our understanding of iNKT cell development and function. Recent transcriptomic studies have uncovered an even greater heterogeneity and challenge our understanding of iNKT cell ontogeny and effector differentiation. We propose a refined model whereby iNKT cells differentiate through a dynamic and continuous instructive process that requires the accumulation and integration of various signals within the thymus or peripheral tissues. Within this framework, we question the existence of true iNKT2 cells and discuss the parallels between mouse and human iNKT cells.

Keywords: iNKT cells; ontogeny; single-cell RNA-sequencing.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation
Humans
Mice
Natural Killer T-Cells*