Distinct gene expression patterns correlate with developmental and functional traits of iNKT subsets.

Hristo Georgiev,Reinhold Förster,Inga Ravens,Günter Bernhardt,Charaf Benarafa

doi:10.1038/ncomms13116

Hristo Georgiev, Reinhold Förster + Show 3 more

Open Access

https://doi.org/10.1038/ncomms13116

Copy DOI

Journal: Nature communications	Publication Date: Oct 10, 2016
Citations: 81	License type: CC BY 4.0

Affiliation: Hannover Medical School, University of Bern

Abstract

Invariant natural killer T (iNKT) cells comprise a subpopulation of innate lymphocytes developing in thymus. A new model proposes subdividing murine iNKT cells into iNKT1, 2 and 17 cells. Here, we use transcriptome analyses of iNKT1, 2 and 17 subsets isolated from BALB/c and C57BL/6 thymi to identify candidate genes that may affect iNKT cell development, migration or function. We show that Fcɛr1γ is involved in generation of iNKT1 cells and that SerpinB1 modulates frequency of iNKT17 cells. Moreover, a considerable proportion of iNKT17 cells express IL-4 and IL-17 simultaneously. The results presented not only validate the usefulness of the iNKT1/2/17-concept but also provide new insights into iNKT cell biology.

Highlights

Invariant natural killer T cells comprise a subpopulation of innate lymphocytes developing in thymus
We identify many genes that are expressed in a subtype specific fashion in both strains and by investigating corresponding mutant mice, we show that Fcer1g and serpinB1 are involved in generating wild type (WT)-like Invariant natural killer T (iNKT) subset compositions
This suggests a high degree of reliability, it should be noted that the low number of replicates, n 1⁄4 2, still represents an element of uncertainty. mRNA data reflecting expression of TBET (Tbx21), PLZF (Zbtb16), and RORg,gt (Rorc) matched expectations (Fig. 1e) and expression patterns of Ccl[5], Il13 as well as Il23r are shown as further examples to demonstrate that the cell sorts were clean enough allowing reliable characterization of iNKT subsets based in their transcriptional profiles (Fig. 1f)

Summary

Introduction

Invariant natural killer T (iNKT) cells comprise a subpopulation of innate lymphocytes developing in thymus. Natural killer T cells can be grouped into several subtypes of which the type I invariant natural killer T (iNKT) cells are most vigorously investigated[1]. INKT cells can influence the outcome of various diseases ranging from bacterial or viral infection[6,7] and cancer[8] to autoimmune and allergy syndromes[9,10]. These findings fostered interest in this highly specialized T cell type that comes into existence in the thymus when T cells pass through the double positive stage of their differentiation. INKT cells express a variety of homing receptors licensing them to migrate to lymphoid and non-lymphoid organs, including skin, liver and lung[18]

Methods

Results

Conclusion