Community Series in the Role of CD1- and MR1-restricted T cells in Immunity and Disease, volume II

Editorial

16 September 2024

Editorial: Community series in the role of CD1- and MR1-restricted T cells in immunity and disease, volume II

Kazuya Iwabuchi

and

Luc Van Kaer

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0 citations

Editors

Luc Van Kaer

Vanderbilt University Medical Center

Kazuya Iwabuchi

Department of Immunology, Kitasato University School of Medicine

Impact

Increased cell death in Eed-deficient iNKT cells is associated with abnormal expression of Cdkn2a and Cdkn1a. (A, B) Representative FACS histograms and percentage of BrdU+ iNKT cells in the thymus from BrdU-pulsed control (n=3) and Eed cKO (n=4) mice. The gray line indicates CD4+CD8-SP cells. (C, D) Representative FACS histograms and percentage of Annexin V+-dead cells in the indicated iNKT cells from control (n=4) and Eed cKO (n=3) mice. (E) ChIP-seq analysis of H3K27me3 in iNKT cells at the Cdkn2a locus (upper) and Cdkn1a locus (lower). (F) ChIP-qPCR analysis of H3K27me3 enrichment at the proximal promoter region of p16, p19, and p21 in sorted thymic CD24-NK1.1- S1/2 iNKT cells from control and Eed cKO mice (n=3 each). (G) Real-time PCR analysis of the expression of p16, p19, and p21 in sorted thymic S2 iNKT cells from control and Eed cKO mice (n=3 each). These expressions were normalized to Ywhaz. Data are mean ± SD with statistical significance determined by unpaired t-test (F, G) or multiple t-tests (B, D). p values are represented as *, <0.05; **, <0.01; ****, <0.0001. Data are representative of at least two independent experiments.

Original Research

20 September 2024

Eed-dependent histone modification orchestrates the iNKT cell developmental program alleviating liver injury

Yun Guo

, 6 more and

Tomoharu Yasuda

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α-GalCer pretreatment expands IL10-producing B cells. WT B6 mice were injected i.p. with α-GalCer (2 μg/mouse) and, seven days later, the spleens and livers were harvested for the following analyses. (A, B) The total CD19+ B cell numbers (A) and the frequency and absolute cell numbers (B) of IL10-producing B cells in the spleen and liver. (C) The frequencies of B cell subsets (FOB, MZB, and B1 cells) in the spleen and liver. (D, E) The frequencies (D) and absolute cell numbers (E) of IL10-producing B cell subsets (FOB, MZB, and B1 cells) in the spleen and liver. (F) Experimental outline: WT B6 mice were injected i.p. with α-GalCer (2 μg/mouse) and, seven days later, splenic CD19+ B cells were isolated by the MACS system. Subsequently, MACS-purified CD19+ B cells (5 × 106 cells/mouse) were adoptively transferred to recipient mice. The recipient mice were injected i.p. with LPS (2 µg/mouse) plus D-GalN (25 mg/mouse) for induction of sepsis. (G) Subsequently, these mice were monitored to evaluate their survival for 3 days after LPS/D-GalN. The mean values ± SD (n = 4 in (A, B, D, E); per group in the experiment; Student’s t-test; *p < 0.05, **p < 0.01, and ***p < 0.001) are shown. The survival rate was analyzed by Kaplan-Meier plots with a log-rank test (*p < 0.05 and **p < 0.01). One representative experiment of two experiments is shown. ns, not significant.

Original Research

17 September 2024

The iNKT cell ligand α-GalCer prevents murine septic shock by inducing IL10-producing iNKT and B cells

Yun Hoo Park

, 4 more and

Seokmann Hong

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Viral interference of the CD1d molecule biosynthesis and recycling pathway. VZV and EBV impede CD1d transcription while HCMV induces CD1d molecular degradation in the enoplasmic reticulum (ER). HIV-1 and HSV-1 both suppress CD1d cell-surface recycling with HIV-1 also being shown to recycle CD1d back to the trans-golgi network (TGN). SARS-CoV-2 induces both proteasomal and lysosomal degradation of CD1d. KSHV induces CD1d endocytosis and internalisation.

Review

17 September 2024

The surveillance of viral infections by the unconventional Type I NKT cell

Varshini Rajashekar

, 3 more and

Allison Abendroth

1,808 views

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Bacterial riboflavin biosynthesizing enzymes, such as ribA and ribD, generate 5-A-RU, which is converted to 5-OP-RU in the presence of methylglyoxal (MGO) (left). CAS is produced by sulfation of cholic acid (CA) by sulfotransferase 2a (Sult2a) in the host. CAS is further taurine-conjugated in the host by bile acid–CoA:amino acid N-acyltransferase (BAAT) or bile acid–CoA synthetase (BACS) to generate TCA7S. Most intestinal bacteria have deconjugation enzymes, bile salt hydrolases (BSH), which metabolize TCA7S to CA7S. Symbiotic bacteria are therefore required for the maintenance of both 5-OP-RU and CA7S.

Mini Review

24 June 2024

Regulation of MAIT cells through host-derived antigens

Emi Ito

and

Sho Yamasaki

2,180 views

0 citations

Comparison of autologous and allogeneic iNKT cells.

Mini Review

19 August 2024

Comparative assessment of autologous and allogeneic iNKT cell transfer in iNKT cell-based immunotherapy

Mariko Takami

and

Shinichiro Motohashi

1,612 views

0 citations

Original Research

22 August 2024

Insights into the CD1 lipidome

Rita Szoke-Kovacs

, 2 more and

Mariolina Salio

1,524 views

1 citations

Mini Review

28 May 2024

Glycolipid antigen recognition by invariant natural killer T cells and its role in homeostasis and antimicrobial responses

Koji Hayashizaki

, 1 more and

Yuki Kinjo

1,233 views

0 citations

Review

13 March 2024

Mucosal-associated invariant T cells in cancer: dual roles, complex interactions and therapeutic potential

Mesut Yigit

, 1 more and

Derya Unutmaz

Mucosal-associated invariant T (MAIT) cells play diverse roles in cancer, infectious diseases, and immunotherapy. This review explores their intricate involvement in cancer, from early detection to their dual functions in promoting inflammation and mediating anti-tumor responses. Within the solid tumor microenvironment (TME), MAIT cells can acquire an ‘exhausted’ state and secrete tumor-promoting cytokines. On the other hand, MAIT cells are highly cytotoxic, and there is evidence that they may have an anti-tumor immune response. The frequency of MAIT cells and their subsets has also been shown to have prognostic value in several cancer types. Recent innovative approaches, such as programming MAIT cells with chimeric antigen receptors (CARs), provide a novel and exciting approach to utilizing these cells in cell-based cancer immunotherapy. Because MAIT cells have a restricted T cell receptor (TCR) and recognize a common antigen, this also mitigates potential graft-versus-host disease (GVHD) and opens the possibility of using allogeneic MAIT cells as off-the-shelf cell therapies in cancer. Additionally, we outline the interactions of MAIT cells with the microbiome and their critical role in infectious diseases and how this may impact the tumor responses of these cells. Understanding these complex roles can lead to novel therapeutic strategies harnessing the targeting capabilities of MAIT cells.

4,370 views

5 citations

In the thymus, NKT0 cells differentiate into CCR7+ iNKT cell progenitors (NKTp). NKTp cells can then emigrate from the thymus to peripheral tissues and undergo further maturation or continue their differentiation into effector subsets, including NKT1, NKT2, or NKT17. IL-15 produced by mTECs drives the development and terminal maturation of C2 iNKT cells in the NKT1 cell population. Although most mature iNKT cells in the thymus are tissue-resident, the C2 iNKT cells exhibit high cytotoxicity with NK cell-like features and circulate among peripheral tissues. Subsequently, C2 iNKT cells serve as the circulating iNKT cells in peripheral tissues, whereas C1 iNKT cells are conventional tissue-resident iNKT cells.

Review

19 February 2024

Insights into the heterogeneity of iNKT cells: tissue-resident and circulating subsets shaped by local microenvironmental cues

Guangwei Cui

, 2 more and

Koichi Ikuta

3,512 views

5 citations

Mini Review

15 February 2024

Contribution of NKT cells and CD1d-expressing cells in obesity-associated adipose tissue inflammation

Masashi Satoh

and

Kazuya Iwabuchi

Natural killer T (NKT) cell are members of the innate-like T lymphocytes and recognizes lipid antigens presented by CD1d-expressing cells. Obesity-associated inflammation in adipose tissue (AT) leads to metabolic dysfunction, including insulin resistance. When cellular communication is properly regulated among AT-residing immune cells and adipocytes during inflammation, a favorable balance of Th1 and Th2 immune responses is achieved. NKT cells play crucial roles in AT inflammation, influencing the development of diet-induced obesity and insulin resistance. NKT cells interact with CD1d-expressing cells in AT, such as adipocytes, macrophages, and dendritic cells, shaping pro-inflammatory or anti-inflammatory microenvironments with distinct characteristics depending on the antigen-presenting cells. Additionally, CD1d may be involved in the inflammatory process independently of NKT cells. In this mini-review, we provide a brief overview of the current understanding of the interaction between immune cells, focusing on NKT cells and CD1d signaling, which control AT inflammation both in the presence and absence of NKT cells. We aim to enhance our understanding of the mechanisms of obesity-associated diseases.

2,902 views

5 citations

Mini Review

19 February 2024

Functions of mucosal associated invariant T cells in eye diseases

Chihiro Fukui

, 12 more and

Kensuke Shibata

1,995 views

0 citations

Activation of MAIT, iNKT, NK, γδ T cells, and conventional T cell was analyzed in 7 participants from group 2 (ALVAC-HIV + AIDSVAX B/E) and 9 participants from group 3 (AIDSVAX B/E).

Brief Research Report

13 February 2024

Innate immune cell activation after HIV-1 vaccine administration is associated with increased antibody production

Kombo F. N’guessan

, 15 more and

Dominic Paquin-Proulx

2,945 views

0 citations

(A) Immature/impaired MAIT cells and/or reduced γδ T cells, possibly caused by microbial dysbiosis, contribute to NEC pathogenesis (39, 48, 49, 112). (B) Change of gut microbiome and innate T cells in preterm infants based on gestation age. The proportions of innate T cells negatively correlate with gestational age. Little is known about whether the innate T cells in preterm infants are of fetal or maternal origin. It is also unclear how the transition of gut microbiome affects the development and function of innate T cells (36, 52, 101, 102). .

Mini Review

08 February 2024

Role of innate T cells in necrotizing enterocolitis

Jianyun Liu

, 5 more and

Troy A. Markel

2,568 views

2 citations

Original Research

01 February 2024

Tumor epitope spreading by a novel multivalent therapeutic cellular vaccine targeting cancer antigens to invariant NKT-triggered dendritic cells in situ

Satoru Yamasaki

, 1 more and

Shin-ichiro Fujii

2,973 views

1 citations

(A) Stimulating iNKT cells with α-GalCer or its analog can either reduce Th1 response or improve Th2 response, potentiate MDSC or M2 macrophage differentiation to improve EAE outcomes. High doses of α-GalCer selectively increase Th1 and Th17 responses to exacerbate EAE progression. Sulfatide activates type II NKT cells, which suppress IFN-γ and IL-4 production by pathogenetic antigen-reactive T cells and protect mice from EAE. (B) IL-17-producing γδ T cells exacerbate EAE progression by increasing inflammation by not only promoting Th17 cell function but also restraining the generation of Tregs. IFNγ-producing γδ T cells suppress the activity of Th17 cells and release chemokines to recruit Treg cells to reduce inflammatory signals. Moreover, γδ T cells can induce the apoptosis of encephalitogenic T cells through Fas/Fas ligand signaling and facilitate recovery from EAE. (C) MAIT cells alleviate the progression of EAE by decreasing inflammatory mediators and increasing IL-10 production. MDSC, myeloid-derived suppressor cell; EAE, experimental autoimmune encephalomyelitis; Treg, regulatory T cells.

Review

03 October 2023

Unconventional T cells in brain homeostasis, injury and neurodegeneration

Mengfei Lv

, 1 more and

Yu Cui

The interaction between peripheral immune cells and the brain is an important component of the neuroimmune axis. Unconventional T cells, which include natural killer T (NKT) cells, mucosal-associated invariant T (MAIT) cells, γδ T cells, and other poorly defined subsets, are a special group of T lymphocytes that recognize a wide range of nonpolymorphic ligands and are the connection between adaptive and innate immunity. Recently, an increasing number of complex functions of these unconventional T cells in brain homeostasis and various brain disorders have been revealed. In this review, we describe the classification and effector function of unconventional T cells, review the evidence for the involvement of unconventional T cells in the regulation of brain homeostasis, summarize the roles and mechanisms of unconventional T cells in the regulation of brain injury and neurodegeneration, and discuss immunotherapeutic potential as well as future research goals. Insight of these processes can shed light on the regulation of T cell immunity on brain homeostasis and diseases and provide new clues for therapeutic approaches targeting brain injury and neurodegeneration.

3,904 views

14 citations

Glycolipid-mediated CD1d engagement triggers the activation of CD1d-expressing non-immune cells (such as IECs and enterochromaffin cells) and immune cells (such as ILC3s, B cells, monocytes and macrophages). This activation occurs through CD1d-intrinsic signaling in non-immune and immune cells and TCR/cytokine-dependent mechanisms in NKT cells. In addition, NKT cells interact with Tregs and neutrophils in a cytokine-dependent manner. Through this cross-talk with diverse cell types, CD1d-restricted NKT cells rapidly produce T helper (Th)1 cytokines (e.g., IFN-γ), Th2 cytokines (e.g., IL-4, IL-5, IL-9, and IL-13), Th17 cytokines (e.g., IL-17 and IL-22), and regulatory cytokines (e.g., IL-10) upon stimulation with various stimuli (e.g., cytokines, chemokines, toll-like receptor (TLR) ligands, fatty acids, and glycolipids), which can elicit either protective or pathogenic effects in CD and UC. CD, Crohn’s disease; UC, ulcerative colitis; IECs, intestinal epithelial cells; ILC3s, type 3 innate lymphoid cells; 5-HT, 5-hydroxytryptamine.

Mini Review

11 January 2024

Role of CD1d and iNKT cells in regulating intestinal inflammation

Sung Won Lee

, 2 more and

Seokmann Hong

3,058 views

1 citations

Review

25 September 2023

Type 1 invariant natural killer T cells in chronic inflammation and tissue fibrosis

Vipin Kumar

, 2 more and

Adam J. Byrne

Chronic tissue inflammation often results in fibrosis characterized by the accumulation of extracellular matrix components remodeling normal tissue architecture and function. Recent studies have suggested common immune mechanisms despite the complexity of the interactions between tissue-specific fibroblasts, macrophages, and distinct immune cell populations that mediate fibrosis in various tissues. Natural killer T (NKT) cells recognizing lipid antigens bound to CD1d molecules have been shown to play an important role in chronic inflammation and fibrosis. Here we review recent data in both experimental models and in humans that suggest a key role of type 1 invariant NKT (iNKT) cell activation in the progression of inflammatory cascades leading to recruitment of neutrophils and activation of the inflammasome, macrophages, fibroblasts, and, ultimately, fibrosis. Emerging evidence suggests that iNKT-associated mechanisms contribute to type 1, type 2 and type 3 immune pathways mediating tissue fibrosis, including idiopathic pulmonary fibrosis (IPF). Thus, targeting a pathway upstream of these immune mechanisms, such as the inhibition of iNKT activation, may be important in modulating various fibrotic conditions.

6,831 views

10 citations