CD138 expression is a molecular signature but not a developmental requirement for RORγt+ NKT17 cells
Shunqun Luo, … , Pyong Woo Park, Jung-Hyun Park
Shunqun Luo, … , Pyong Woo Park, Jung-Hyun Park
Published September 22, 2021
Citation Information: JCI Insight. 2021;6(18):e148038. https://doi.org/10.1172/jci.insight.148038.
View: Text | PDF
Research Article Immunology

CD138 expression is a molecular signature but not a developmental requirement for RORγt+ NKT17 cells

Abstract

Invariant NKT (iNKT) cells are potent immunomodulatory cells that acquire effector function during their development in the thymus. IL-17–producing iNKT cells are commonly referred to as NKT17 cells, and they are unique among iNKT cells to express the heparan sulfate proteoglycan CD138 and the transcription factor RORγt. Whether and how CD138 and RORγt contribute to NKT17 cell differentiation, and whether there is an interplay between RORγt and CD138 expression to control iNKT lineage fate, remain mostly unknown. Here, we showed that CD138 expression was only associated with and not required for the differentiation and IL-17 production of NKT17 cells. Consequently, CD138-deficient mice still generated robust numbers of IL-17–producing RORγt+ NKT17 cells. Moreover, forced expression of RORγt significantly promoted the generation of thymic NKT17 cells, but did not induce CD138 expression on non-NKT17 cells. These results indicated that NKT17 cell generation and IL-17 production were driven by RORγt, employing mechanisms that were independent of CD138. Therefore, our study effectively dissociated CD138 expression from the RORγt-driven molecular pathway of NKT17 cell differentiation.

Authors

Shunqun Luo, Juntae Kwon, Assiatu Crossman, Pyong Woo Park, Jung-Hyun Park

×

Figure 7

iNKT subset differentiation in RORγtTg C57BL/6 mice.

Options: View larger image (or click on image) Download as PowerPoint
iNKT subset differentiation in RORγtTg C57BL/6 mice. (A) CD138 expressi...
(A) CD138 expression on thymic iNKT cells of RORγtTg and WT littermate C57BL/6 mice. The dot plots identify and show the frequency of thymic iNKT cells (top), and the histograms show CD138 expression among iNKT cells of C57BL/6 mice (bottom). The graphs show the frequency of iNKT cells among total thymocytes (left) and the frequency of CD138+ cells among thymic iNKT cells (right). Data summarize 6 independent experiments with a total of 12 RORγtTg and 13 WT littermate C57BL/6 mice. (B) Thymic iNKT subset composition of RORγtTg and WT littermate C57BL/6 mice. The dot plots show the frequencies of each iNKT subset identified by PLZF versus RORγt and PLZF versus T-bet staining (left). The graphs show the frequencies of NKT1, NKT2, and NKT17 cells among thymic mature iNKT cells (right). Data summarize 3 independent experiments with a total of 5 RORγtTg and 7 WT littermate C57BL/6 mice. (C) RORγt and CD138 expression in T-bet+ NKT1 cells of RORγtTg and WT littermate C57BL/6 mice. Histograms show RORγt and CD138 expression in thymic NKT1 cells (left). The graphs show the MFI of RORγt and CD138 expression in thymic NKT1 cells of the indicated mice (right). Data summarize 2 independent experiments with a total of 4 RORγtTg and 5 WT littermate C57BL/6 mice. All data are presented as mean ± SEM. P values were determined by unpaired 2-tailed Student’s t test. **P < 0.01; ***P < 0.001; NS, not significant.