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Review
. 2018 Jun 26:9:1450.
doi: 10.3389/fimmu.2018.01450. eCollection 2018.

"V体育平台登录" How Lipid-Specific T Cells Become Effectors: The Differentiation of iNKT Subsets

Haiguang Wang  1 , Kristin A Hogquist  1
Affiliations
Review

How Lipid-Specific T Cells Become Effectors: The Differentiation of iNKT Subsets

VSports手机版 - Haiguang Wang et al. Front Immunol. .

"V体育ios版" Abstract

In contrast to peptide-recognizing T cells, invariant natural killer T (iNKT) cells express a semi-invariant T cell receptor that specifically recognizes self- or foreign-lipids presented by CD1d molecules. There are three major functionally distinct effector states for iNKT cells. Owning to these innate-like effector states, iNKT cells have been implicated in early protective immunity against pathogens. Yet, growing evidence suggests that iNKT cells play a role in tissue homeostasis as well. In this review, we discuss current knowledge about the underlying mechanisms that regulate the effector states of iNKT subsets, with a highlight on the roles of a variety of transcription factors and describe how each subset influences different facets of thymus homeostasis. VSports手机版.

Keywords: development; invariant natural killer T cell; lipid; mucosal-associated invariant T cell; subsets; thymus V体育安卓版. .

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Figures

Figure 1
Figure 1
The selection, specification, and effector differentiation of invariant natural killer T (iNKT) cells in the thymus. The initial positive selection of iNKT cells depends on the interaction among double-positive thymocytes in cortex. Then, with the upregulation of PLZF and the chemokine receptor CCR7, the multi-potent iNKT common precursors migrate to thymic medulla and specify their fate into different effector subsets. The effector differentiation into NKT1, NKT2, and NKT17 are influenced and directed by various factors. For instance, cytokine signals play essential roles in differentiation: IL-15 is critical for CD122 expressing NKT1 cell differentiation, whereas TGF-β is required for TGF-βR-expressing NKT17 cells, while NKT2 cells express IL-17 RB (IL-25 receptor), although the role of IL-25 requires evaluation. iNKT subsets are poised in an effector state, but only NKT2 cells are actively producing cytokine (IL-4) at steady state, while NKT1 and NKT17 cells maintain potential to produce IFN-γ or IL-17, respectively, after stimulation.
Figure 2
Figure 2
The invariant natural killer T (iNKT) effector subsets modulate immune homeostasis in the thymic medulla. The iNKT effector subsets predominantly reside in the thymic medullary area. Both NKT2 and NKT17 cells express RANK ligand, which interacts with RANK on medullary thymic epithelial (mTEC) to induce Aire expression. NKT2 cells also produce IL-4 at steady state, which has a striking effect on CD8+ single positive thymocytes—causing them to upregulate Eomes and adopt memory-like phenotype and function. The iNKT-derived type 2 cytokines, IL-4 and IL-13, also influence mTEC to promote emigration of mature thymocytes, through and as-yet undefined mechanism. The activation requirements for NKT2 cells are poorly defined, although they do need T cell receptor stimulation to produce IL-4 in the medulla.
Figure 3
Figure 3
The lineage-diversification model of invariant natural killer T (iNKT) cell development parallels that of mucosal-associated invariant T (MAIT) cells. Interactions between double-positive (DP) thymocytes expressing the appropriate T cell receptor and CD1d or MR1 on neighboring thymocytes generates CD24+ CD44− lineage committed stage 0 cells (Selection). With downregulation of CD24 and upregulation of the signature transcription factor PLZF, PLZFhigh progenitor cells migrate from cortex to medulla, likely mediated by the chemokine receptor CCR7 (Specification). In the medulla, responding to various cues, the PLZFhigh CCR7+ progenitor further differentiates into distinct effector subsets (Effector differentiation). Thus, the thymic development of iNKT cells and MAIT cells are parallel in many aspects except that an IL-4/13-producing MAIT cell has not been described.
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