Natural Killer T-Cells

Publication Title: 
The Journal of Biological Chemistry

Invariant natural killer T (iNKT) cells are a unique subset of innate T lymphocytes that are selected by CD1d. They have diverse immune regulatory functions via the rapid production of interferon-γ (IFN-γ) and interleukin-4 (IL-4). In the absence of signaling nodes Itk and Txk, Tec family non-receptor tyrosine kinases, mice exhibit a significant block in iNKT cell development. We now show here that although the Itk node is required for iNKT cell maturation, the kinase domain edge of Itk is not required for continued maturation iNKT cells in the thymus compared with Itk-null mice.

Author(s): 
Qi, Qian
Xia, Mingcan
Bai, Yuting
Yu, Sanhong
Cantorna, Margherita
August, Avery
Publication Title: 
Annals of the New York Academy of Sciences

Vitamin D is an important regulator of immune function. T cells express the vitamin D receptor (VDR) and have been shown to be direct and indirect vitamin D targets. Why should T cells be responsive to vitamin D? The data suggest that expression of the VDR is required for the development of two cell types, NKT cells and CD8αα T cells, which inhibit autoimmunity. In addition, effector T cell cytokine production is regulated by vitamin D.

Author(s): 
Cantorna, Margherita T.
Publication Title: 
Journal of Immunology (Baltimore, Md.: 1950)

Vitamin D status changes with season, but the effect of these changes on immune function is not clear. In this study, we show that in utero vitamin D deficiency in mice results in a significant reduction in invariant NKT (iNKT) cell numbers that could not be corrected by later intervention with vitamin D or 1,25-dihydroxy vitamin D(3) (active form of the vitamin). Furthermore, this was intrinsic to hematopoietic cells, as vitamin D-deficient bone marrow is specifically defective in generating iNKT cells in wild-type recipients.

Author(s): 
Yu, Sanhong
Cantorna, Margherita T.
Publication Title: 
Infection and Immunity

There are two important mechanisms of activation of invariant natural killer T cells (iNKT cells) by microbes: direct activation of the invariant T-cell receptor (TCR) by microbial glycolipids presented by CD1d and indirect activation, mediated by the responses of antigen-presenting cells to microbes.

Author(s): 
Rieder, Sadiye Amcaoglu
Nagarkatti, Prakash
Nagarkatti, Mitzi
Publication Title: 
Journal of Immunology (Baltimore, Md.: 1950)

Vitamin D receptor (VDR) deficiency (knockout [KO]) results in a failure of mice to generate an airway hyperreactivity (AHR) response on both the BALB/c and C57BL/6 background. The cause of the failed AHR response is the defective population of invariant NKT (iNKT) cells in the VDR KO mice because wild-type (WT) iNKT cells rescued the AHR response. VDR KO mice had significantly fewer iNKT cells and normal numbers of T cells in the spleen compared with WT mice. In BALB/c VDR KO mice, the reduced frequencies of iNKT cells were not apparent in the liver or thymus.

Author(s): 
Yu, Sanhong
Zhao, Jun
Cantorna, Margherita T.
Publication Title: 
Molecular Aspects of Medicine

Low vitamin D status is associated with an increased risk of immune-mediated diseases like inflammatory bowel disease (IBD) in humans. Experimentally vitamin D status is a factor that shapes the immune response. Animals that are either vitamin D deficient or vitamin D receptor (VDR) deficient are prone to develop IBD. Conventional T cells develop normally in VDR knockout (KO) mice but over-produce IFN-γ and IL-17. Naturally occurring FoxP3+ regulatory T cells are present in normal numbers in VDR KO mice and function as well as wildtype T regs.

Author(s): 
Ooi, Jot Hui
Chen, Jing
Cantorna, Margherita T.
Publication Title: 
Journal of Immunology (Baltimore, Md.: 1950)

Patients suffering from ulcerative colitis (UC) exhibit chronic colonic inflammation caused by a dysregulated mucosal immune response and epithelial barrier disruption. Th2 cytokines, including IL-13, have been implicated in the pathogenesis of UC. IL-13 induces phosphorylation of STAT6, and we previously demonstrated increased epithelial p-STAT6 in children with UC. In this study, we investigated the role of STAT6 in oxazolone colitis, a murine model of UC, by inducing colitis in STAT6-deficient (STAT6(-/-)) and wild type (WT) mice.

Author(s): 
Rosen, Michael J.
Chaturvedi, Rupesh
Washington, M. Kay
Kuhnhein, Lindsay A.
Moore, Preston D.
Coggeshall, Scott S.
McDonough, Elizabeth M.
Weitkamp, Jörn-Hendrik
Singh, Amar B.
Coburn, Lori A.
Williams, Christopher S.
Yan, Fang
Van Kaer, Luc
Peebles, R. Stokes
Wilson, Keith T.
Publication Title: 
Journal of Immunology (Baltimore, Md.: 1950)

Invariant NKT (iNKT) cells are a subset of T lymphocytes that recognize glycolipid Ags presented by the MHC class I-related protein CD1d. Activation of iNKT cells with glycolipid Ags, such as the marine sponge-derived reagent α-galactosylceramide (α-GalCer), results in the rapid production of a variety of cytokines and activation of many other immune cell types.

Author(s): 
Parekh, Vrajesh V.
Wu, Lan
Olivares-Villagómez, Danyvid
Wilson, Keith T.
Van Kaer, Luc
Publication Title: 
Journal of Immunology (Baltimore, Md.: 1950)

Regulation and induction of anergy in NKT cells of the liver can inhibit autoimmune and antitumor responses by mechanisms that are poorly understood. We investigated the effects of PGE2, delivered by intestinal, mucus-derived, exosome-like nanoparticles (IDENs), on NKT cells in mice. In this study, we demonstrate that IDENs migrate to the liver where they induce NKT cell anergy. These effects were mediated by an IDENs' PGE2.

Author(s): 
Deng, Zhong-Bin
Zhuang, Xiaoying
Ju, Songwen
Xiang, Xiaoyu
Mu, Jingyao
Liu, Yuelong
Jiang, Hong
Zhang, Lifeng
Mobley, James
McClain, Craig
Feng, Wenke
Grizzle, William
Yan, Jun
Miller, Donald
Kronenberg, Mitchell
Zhang, Huang-Ge
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