Atopic Dermatitis Lesions Accommodate Low Numbers of Invariant Natural Killer T (NKT) Cells Expressing Interleukin-4 and Interferon-gamma

2009 ◽  
Vol 123 (2) ◽  
pp. S37-S37
Author(s):  
D. Simon ◽  
E. Kozlowski ◽  
H.U. Simon
Keyword(s):  
Atopic Dermatitis ◽  
Natural Killer ◽  
Interferon Gamma ◽  
Nkt Cells ◽  
Interleukin 4 ◽  
Invariant Natural Killer ◽  
Natural Killer T

scholarly journals Type I Natural Killer T Cells as Key Regulators of the Immune Response to Infectious Diseases

2020 ◽  
Vol 34 (2) ◽  
pp. e00232-20
Author(s):  
Nicolás M. S. Gálvez ◽  
Karen Bohmwald ◽  
Gaspar A. Pacheco ◽  
Catalina A. Andrade ◽  
Leandro J. Carreño ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Infectious Diseases ◽  
Natural Killer ◽  
Nkt Cells ◽  
Interleukin 4 ◽  
Type I ◽  
Inkt Cells ◽  
Class I Mhc ◽  
Natural Killer T

SUMMARYThe immune system must work in an orchestrated way to achieve an optimal response upon detection of antigens. The cells comprising the immune response are traditionally divided into two major subsets, innate and adaptive, with particular characteristics for each type. Type I natural killer T (iNKT) cells are defined as innate-like T cells sharing features with both traditional adaptive and innate cells, such as the expression of an invariant T cell receptor (TCR) and several NK receptors. The invariant TCR in iNKT cells interacts with CD1d, a major histocompatibility complex class I (MHC-I)-like molecule. CD1d can bind and present antigens of lipid nature and induce the activation of iNKT cells, leading to the secretion of various cytokines, such as gamma interferon (IFN-γ) and interleukin 4 (IL-4). These cytokines will aid in the activation of other immune cells following stimulation of iNKT cells. Several molecules with the capacity to bind to CD1d have been discovered, including α-galactosylceramide. Likewise, several molecules have been synthesized that are capable of polarizing iNKT cells into different profiles, either pro- or anti-inflammatory. This versatility allows NKT cells to either aid or impair the clearance of pathogens or to even control or increase the symptoms associated with pathogenic infections. Such diverse contributions of NKT cells to infectious diseases are supported by several publications showing either a beneficial or detrimental role of these cells during diseases. In this article, we discuss current data relative to iNKT cells and their features, with an emphasis on their driving role in diseases produced by pathogenic agents in an organ-oriented fashion.

Relevance of sexual dimorphism to regulatory T cells: estradiol promotes IFN-γ production by invariant natural killer T cells

Blood ◽  
2005 ◽  
Vol 105 (6) ◽  
pp. 2415-2420 ◽  
Author(s):  
Pierre Gourdy ◽  
Luiza M. Araujo ◽  
Ren Zhu ◽  
Barbara Garmy-Susini ◽  
Séverine Diem ◽  
...  
Keyword(s):  
T Cells ◽  
Natural Killer ◽  
Interleukin 4 ◽  
Response To Treatment ◽  
Inkt Cells ◽  
Gender Dimorphism ◽  
Ifn Γ ◽  
Invariant Natural Killer ◽  
Natural Killer T

Abstract Mechanisms accounting for gender dimorphism during immune responses are still poorly understood. Since invariant natural killer T (iNKT) cells exert important regulatory functions through their capacity to produce both T helper 1 (Th1) and Th2 cytokines, we addressed the question of whether these activities could be modulated by sexual hormones. We found that in vivo challenge with the specific ligand of iNKT cells, α-galactosylceramide (α-GalCer), induced significantly higher concentrations of interferon γ (IFN-γ) in the serum of female than in that of male mice, while interleukin 4 (IL-4) production was not modified. In support of a crucial role of ovarian hormones in this phenomenon, a significant decrease of serum IFN-γ concentrations occurred in ovariectomized females, in response to treatment with α-GalCer, while orchidectomy affected neither IFN-γ nor IL-4 serum concentrations in males. The implication of estrogens in this selective enhancement of IFN-γ production by iNKT cells was demonstrated by (1) the increased α-GalCer–induced IFN-γ synthesis by iNKT cells upon both in vitro and in vivo exposure to estradiol and (2) the abolition of the sex-linked difference in α-GalCer–induced IFN-γ release in estrogen receptor α-deficient mice. These results provide the first evidence that estrogens influence iNKT cells leading to this gender dimorphism in their cytokine production profile.

scholarly journals CD1d-restricted Help To B Cells By Human Invariant Natural Killer T Lymphocytes

2003 ◽  
Vol 197 (8) ◽  
pp. 1051-1057 ◽  
Author(s):  
Grazia Galli ◽  
Sandra Nuti ◽  
Simona Tavarini ◽  
Luisa Galli-Stampino ◽  
Claudia De Lalla ◽  
...  
Keyword(s):  
B Cells ◽  
T Lymphocytes ◽  
Natural Killer ◽  
Nkt Cells ◽  
Immunoglobulin Production ◽  
Direct Role ◽  
Invariant Nkt Cells ◽  
Invariant Natural Killer ◽  
Natural Killer T

Invariant natural killer T (NKT) cells are a highly conserved subset of T lymphocytes expressing a semi-invariant T cell receptor (TCR), which is restricted to CD1d and specific for the glycosphingolipid antigen α-galactosylceramide. Their ability to secrete a variety of cytokines, which in turn modulate the activation of cells of both innate and acquired immune responses, suggests that invariant NKT cells exert a regulatory role mainly via indirect mechanisms. A relevant question is whether invariant NKT cells can directly help B cells. We document here that human invariant NKT cells are as efficient as conventional CD4+ Th0 lymphocytes in promoting proliferation of autologous memory and naive B lymphocytes in vitro, and in inducing immunoglobulin production. Help to B cells by invariant NKT cells is CD1d-dependent and delivered also in the absence of α-galactosylceramide, suggesting that NKT cells recognize an endogenous ligand presented by CD1d on B cells. The two major subsets of invariant NKT cells, CD4+ and double negative (CD4−CD8−), express comparable levels of CD40 ligand and cytokines, but differ in helper functions. Indeed, both subsets induce similar levels of B cell proliferation, whereas CD4+ NKT cells induce higher levels of immunoglobulin production. These results suggest a direct role for invariant NKT cells in regulating B lymphocyte proliferation and effector functions.

scholarly journals Combined proinflammatory cytokine and cognate activation of invariant natural killer T cells enhances anti-DNA antibody responses

2020 ◽  
Vol 117 (16) ◽  
pp. 9054-9063 ◽  
Author(s):  
Saikiran K. Sedimbi ◽  
Thomas Hägglöf ◽  
Manasa G. Garimella ◽  
Shan Wang ◽  
Amanda Duhlin ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Natural Killer ◽  
Chronic Inflammation ◽  
Cell Activation ◽  
Fas Ligand ◽  
Nkt Cells ◽  
Autoreactive B Cells ◽  
Invariant Natural Killer ◽  
Natural Killer T

Invariant natural killer T (iNKT) cells serve as early rapid responders in the innate immune response to self-derived autoantigens and pathogen-derived danger signals and antigens. iNKT cells can serve both as helpers for effector B cells and negatively regulate autoreactive B cells. Specifically, iNKT cells drive B cell proliferation, class switch, and antibody production to induce primary antigen-specific immune responses. On the other hand, inflammasome-mediated activation drives accumulation of neutrophils, which license iNKT cells to negatively regulate autoreactive B cells via Fas ligand (FasL). This positions iNKT cells at an apex to support or inhibit B cell responses in inflammation. However, it is unknown which effector mechanism dominates in the face of cognate glycolipid activation during chronic inflammation, as might result from glycolipid vaccination or infection during chronic autoimmune disease. We stimulated iNKT cells by cognate glycolipid antigen α-galactosylceramide (αGalCer) and measured B cell activation during interleukin 18 (IL-18)-induced chronic inflammation. Moreover, glycolipid-activated iNKT cells increased the serum concentration of autoantibodies, frequency of germinal center (GC) B cells, and antigen-specific plasma cells induced during chronic IL-18–mediated inflammation, as compared with IL-18 alone. Further, activation of iNKT cells via cognate glycolipid during IL-18–mediated inflammation overrides the licensing function of neutrophils, instead inducing iNKT follicular helper (iNKTfh) cells that in turn promote autoimmunity. Thus, our data demonstrate that glycolipids which engage iNKT cells support antigen-specific B cell help during inflammasome-mediated inflammation.

scholarly journals Immunoporosis: A New Role for Invariant Natural Killer T (NKT) Cells Through Overexpression of Nuclear Factor-κB Ligand (RANKL)

2019 ◽  
Vol 25 ◽  
pp. 2151-2158 ◽  
Author(s):  
Konstantinos Tilkeridis ◽  
Georgios Kiziridis ◽  
Athanasios Ververidis ◽  
Menelaos Papoutselis ◽  
Ioannis Kotsianidis ◽  
...  
Keyword(s):  
Natural Killer ◽  
Nkt Cells ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Invariant Natural Killer ◽  
Natural Killer T

scholarly journals Transcriptome and Function of Novel Immunosuppressive Autoreactive Invariant Natural Killer T Cells That Are Absent in Progressive Multiple Sclerosis

2021 ◽  
Vol 8 (6) ◽  
pp. e1065
Author(s):  
Belinda Carrión ◽  
Yawei Liu ◽  
Mahdieh Hadi ◽  
Jon Lundstrom ◽  
Jeppe Romme Christensen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Natural Killer ◽  
Protein Level ◽  
Fas Ligand ◽  
Nkt Cells ◽  
Tnf Receptor ◽  
Inkt Cells ◽  
Invariant Natural Killer ◽  
Natural Killer T

Background and ObjectiveThe aim of this study was to determine whether natural killer T (NKT) cells, including invariant (i) NKT cells, have clinical value in preventing the progression of multiple sclerosis (MS) by examining the mechanisms by which a distinct self-peptide induces a novel, protective invariant natural killer T cell (iNKT cell) subset.MethodsWe performed a transcriptomic and functional analysis of iNKT cells that were reactive to a human collagen type II self-peptide, hCII707-721, measuring differentially induced genes, cytokines, and suppressive capacity.ResultsWe report the first transcriptomic profile of human conventional vs novel hCII707-721–reactive iNKT cells. We determined that hCII707-721 induces protective iNKT cells that are found in the blood of healthy individuals but not progressive patients with MS (PMS). By transcriptomic analysis, we observed that hCII707-721 promotes their development and proliferation, favoring the splicing of full-length AKT serine/threonine kinase 1 (AKT1) and effector function of this unique lineage by upregulating tumor necrosis factor (TNF)-related genes. Furthermore, hCII707-721–reactive iNKT cells did not upregulate interferon (IFN)-γ, interleukin (IL)-4, IL-10, IL-13, or IL-17 by RNA-seq or at the protein level, unlike the response to the glycolipid alpha-galactosylceramide. hCII707-721–reactive iNKT cells increased TNFα only at the protein level and suppressed autologous-activated T cells through FAS-FAS ligand (FAS-FASL) and TNFα-TNF receptor I signaling but not TNF receptor II.DiscussionBased on their immunomodulatory properties, NKT cells have a potential value in the treatment of autoimmune diseases, such as MS. These significant findings suggest that endogenous peptide ligands can be used to expand iNKT cells, without causing a cytokine storm, constituting a potential immunotherapy for autoimmune conditions, including PMS.

scholarly journals Altered Peripheral Invariant Natural Killer T Cells in Atopic Dermatitis

2011 ◽  
Vol 31 (5) ◽  
pp. 864-872 ◽  
Author(s):  
Edit Gyimesi ◽  
Georgina Nagy ◽  
Éva Remenyik ◽  
Sándor Sipka ◽  
Margit Zeher ◽  
...  
Keyword(s):  
T Cells ◽  
Atopic Dermatitis ◽  
Natural Killer ◽  
Natural Killer T Cells ◽  
Killer T Cells ◽  
Invariant Natural Killer ◽  
Natural Killer T
Sign in / Sign up

Export Citation Format

Share Document