Year-end Sale % OFF 
Abstract
Invariant natural killer T (iNKT) cells play important roles in bridging innate and adaptive immunity via rapidly producing a variety of cytokines. A small subset of iNKT cells produces IL-17 and is generated in the thymus during iNKT-cell ontogeny. The mechanisms that control the development of these IL-17-producing iNKT-17 cells (iNKT-17) are still not well defined. Diacylglycerol kinase ζ (DGKζ) belongs to a family of enzymes that catalyze the phosphorylation and conversion of diacylglycerol to phosphatidic acid, two important second messengers involved in signaling from numerous receptors. We report here that DGKζ plays an important role in iNKT-17 development. A deficiency of DGKζ in mice causes a significant reduction of iNKT-17 cells, which is correlated with decreased RORγt and IL-23 receptor expression. Interestingly, iNKT-17 defects caused by DGKζ deficiency can be corrected in chimeric mice reconstituted with mixed wild-type and DGKζ-deficient bone marrow cells. Taken together, our data identify DGKζ as an important regulator of iNKT-17 development through iNKT-cell extrinsic mechanisms.
Highlights
Invariant natural killer T cells represent a unique Tcell lineage with the ability to bridge innate and adaptive immune responses [1,2,3,4]. iNKT cells express the invariant Vα14-Jα18 TCR in mice and the Vα24-Jα18 TCR in humans, with limited TCRVβ usages. iNKT cells are positively selected in the thymus after the engagement of the iVα14TCR with glycolipids presented by CD1d expressed on CD4+CD8+ double-positive (DP) thymocytes [5,6,7,8]
INKT cells capable of producing the IL-17 family of cytokines, such as IL-17A, IL-17F, and IL-22, have been identified [15,16,17,18]. iNKT cell-derived IL-17-family cytokines are implicated in both inflammatory responses such as airway inflammation via recruiting neutrophils and protective roles such as suppression of liver inflammation [19,20]. iNKT-17 cells are generated in the thymus and are considered to be developmentally programmed [17,21]. iNKT-17 cells are mainly restricted to the NK1.1- CD4- population [15] and express the marker for recent thymic emigrant and nature-regulatory T cells neuropilin-1 [16]
We compared the expression of these isoforms between conventional αβ T (cαβT) cells and iNKT cells
Summary
Invariant natural killer T (iNKT) cells represent a unique Tcell lineage with the ability to bridge innate and adaptive immune responses [1,2,3,4]. iNKT cells express the invariant Vα14-Jα18 TCR (iVα14TCR) in mice and the Vα24-Jα18 TCR in humans, with limited TCRVβ usages. iNKT cells are positively selected in the thymus after the engagement of the iVα14TCR with glycolipids presented by CD1d expressed on CD4+CD8+ double-positive (DP) thymocytes [5,6,7,8]. Invariant natural killer T (iNKT) cells represent a unique Tcell lineage with the ability to bridge innate and adaptive immune responses [1,2,3,4]. INKT cells express the invariant Vα14-Jα18 TCR (iVα14TCR) in mice and the Vα24-Jα18 TCR in humans, with limited TCRVβ usages. INKT cells are positively selected in the thymus after the engagement of the iVα14TCR with glycolipids presented by CD1d expressed on CD4+CD8+ double-positive (DP) thymocytes [5,6,7,8]. INKT cell-derived IL-17-family cytokines are implicated in both inflammatory responses such as airway inflammation via recruiting neutrophils and protective roles such as suppression of liver inflammation [19,20]. INKT-17 cells are generated in the thymus and are considered to be developmentally programmed [17,21]. It has become clear that iNKT-17 represents a unique iNKT sublineage with important functions in the pathogenesis of diseases, the signal control for the generation/maintenance of this sublineage of iNKT cells is not well understood
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
