CD138 expression is a molecular signature but not a developmental requirement for RORγt+ NKT17 cells
Shunqun Luo, Juntae Kwon, Assiatu Crossman, Pyong Woo Park, Jung-Hyun Park
Shunqun Luo, Juntae Kwon, Assiatu Crossman, Pyong Woo Park, Jung-Hyun Park
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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

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Figure 6

Lack of innate CD8 T cells in RORγtTg BALB/c thymocytes.

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Lack of innate CD8 T cells in RORγtTg BALB/c thymocytes. (A) T cell deve...
(A) T cell development in the thymus of RORγtTg BALB/c mice. Mature thymocytes were identified by high levels of TCRβ expression and then further assessed for CD4 and CD8 coreceptor expression. Histograms and contour plots (left) are representative, and the graph showing the frequency of CD8SP T cells (right) is a summary of 3 independent experiments with a total of 9 RORγtTg and 6 WT littermate BALB/c mice. (B) Innate-type marker expression and cell numbers of CD8SP thymocytes of RORγtTg BALB/c mice. CD44 versus CXCR3 and CD44 versus CD122 expression profiles and the frequencies and numbers of innate-type cells were assessed in TCRβhi CD8SP thymocytes of RORγtTg and WT littermate BALB/c mice. The contour plots represent and the graphs summarize 2 independent experiments with a total of 6 RORγtTg and 6 WT littermate BALB/c mice. (C) Intranuclear staining for Eomes in mature CD8SP thymocytes of RORγtTg and WT littermate BALB/c mice. The histogram is representative of 2 independent experiments with a total of 4 RORγtTg and 3 WT littermate BALB/c mice. (D) IFN-γ production by mature CD8SP cells of RORγtTg and WT littermate BALB/c thymocytes that were stimulated with PMA and ionomycin for 5 hours in the presence of brefeldin A. Data summarize 2 independent experiments with a total of 4 RORγtTg and 3 WT littermate BALB/c mice. All data are presented as mean ± SEM. P values were determined by 2-tailed unpaired Student’s t test. *P < 0.05; ***P < 0.001.