scholarly journals Effects of Invariant NKT Cells on Parasite Infections and Hygiene Hypothesis

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Jun-Qi Yang ◽  
Yonghua Zhou ◽  
Ram Raj Singh
Keyword(s):  
Hygiene Hypothesis ◽  
Lymphoid Cells ◽  
Parasitic Infections ◽  
Inkt Cells ◽  
Invariant Nkt Cells ◽  
Natural Ligands ◽  
Parasite Infections ◽  
Underlying Mechanisms ◽  
Invariant Natural Killer

Invariant natural killer T (iNKT) cells are unique subset of innate-like T cells recognizing glycolipids. iNKT cells can rapidly produce copious amounts of cytokines upon antigen stimulation and exert potent immunomodulatory activities for a wide variety of immune responses and diseases. We have revealed the regulatory effect of iNKT cells on autoimmunity with a serial of publications. On the other hand, the role of iNKT cells in parasitic infections, especially in recently attractive topic “hygiene hypothesis,” has not been clearly defined yet. Bacterial and parasitic cell wall is a cellular structure highly enriched in a variety of glycolipids and lipoproteins, some of which may serve as natural ligands of iNKT cells. In this review, we mainly summarized the recent findings on the roles and underlying mechanisms of iNKT cells in parasite infections and their cross-talk with Th1, Th2, Th17, Treg, and innate lymphoid cells. In most cases, iNKT cells exert regulatory or direct cytotoxic roles to protect hosts against parasite infections. We put particular emphasis as well on the identification of the natural ligands from parasites and the involvement of iNKT cells in the hygiene hypothesis.

Role of NKT Cells in the Digestive System. I. Invariant NKT cells and liver diseases: is there strength in numbers?

2007 ◽  
Vol 293 (4) ◽  
pp. G651-G656 ◽  
Author(s):  
Maureen N. Ajuebor
Keyword(s):  
Liver Diseases ◽  
Animal Studies ◽  
Inflammatory Responses ◽  
Nkt Cells ◽  
Vital Role ◽  
Controversial Issues ◽  
Inkt Cells ◽  
Invariant Nkt Cells ◽  
Invariant Natural Killer

Information regarding the functional role of the innate immune T cell, invariant natural killer T (iNKT) cells, in the pathophysiology of liver diseases continues to emerge. Results from animal studies suggest that iNKT cells can have divergent roles by specifically promoting the development of proinflammatory or anti-inflammatory responses in liver diseases. In this themes article, I discuss the critical evidence from animal models that demonstrate a vital role for iNKT cells in the pathophysiology of liver diseases with emphasis on viral, autoimmune, and toxin-induced liver diseases. Furthermore, I discuss the controversial issues (including iNKT cell apoptosis) that typify some of these studies. Finally, I highlight areas that require additional investigation.

scholarly journals Revisiting the Hygiene Hypothesis in the Context of Autoimmunity

2021 ◽  
Vol 11 ◽  
Author(s):  
Jean-François Bach
Keyword(s):  
Molecular Mechanisms ◽  
Epidemiological Data ◽  
Allergic Diseases ◽  
Hygiene Hypothesis ◽  
Interleukin 10 ◽  
Major Question ◽  
Important Place ◽  
Immunoregulatory Cytokines ◽  
Underlying Mechanisms

Initially described for allergic diseases, the hygiene hypothesis was extended to autoimmune diseases in the early 2000s. A historical overview allows appreciation of the development of this concept over the last two decades and its discussion in the context of evolution. While the epidemiological data are convergent, with a few exceptions, the underlying mechanisms are multiple and complex. A major question is to determine what is the respective role of pathogens, bacteria, viruses, and parasites, versus commensals. The role of the intestinal microbiota has elicited much interest, but is it a cause or a consequence of autoimmune-mediated inflammation? Our hypothesis is that both pathogens and commensals intervene. Another question is to dissect what are the underlying cellular and molecular mechanisms. The role of immunoregulatory cytokines, in particular interleukin-10 and TGF beta is probably essential. An important place should also be given to ligands of innate immunity receptors present in bacteria, viruses or parasites acting independently of their immunogenicity. The role of Toll-Like Receptor (TLR) ligands is well documented including via TLR ligand desensitization.

scholarly journals iNKT cell development is orchestrated by different branches of TGF-β signaling

2009 ◽  
Vol 206 (6) ◽  
pp. 1365-1378 ◽  
Author(s):  
Jean-Marc Doisne ◽  
Laurent Bartholin ◽  
Kai-Ping Yan ◽  
Céline N. Garcia ◽  
Nadia Duarte ◽  
...  
Keyword(s):  
Cell Development ◽  
Inkt Cell ◽  
Maturation Stage ◽  
Inkt Cells ◽  
Signaling Function ◽  
Regulatory Functions ◽  
Invariant Natural Killer ◽  
Fine Tune

Invariant natural killer T (iNKT) cells constitute a distinct subset of T lymphocytes exhibiting important immune-regulatory functions. Although various steps of their differentiation have been well characterized, the factors controlling their development remain poorly documented. Here, we show that TGF-β controls the differentiation program of iNKT cells. We demonstrate that TGF-β signaling carefully and specifically orchestrates several steps of iNKT cell development. In vivo, this multifaceted role of TGF-β involves the concerted action of different pathways of TGF-β signaling. Whereas the Tif-1γ branch controls lineage expansion, the Smad4 branch maintains the maturation stage that is initially repressed by a Tif-1γ/Smad4-independent branch. Thus, these three different branches of TGF-β signaling function in concert as complementary effectors, allowing TGF-β to fine tune the iNKT cell differentiation program.

scholarly journals Infection with Toxocara canis Inhibits the Production of IgE Antibodies to α-Gal in Humans: Towards a Conceptual Framework of the Hygiene Hypothesis?

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 167 ◽  
Author(s):  
Adnan Hodžić ◽  
Lourdes Mateos-Hernández ◽  
Emilie Fréalle ◽  
Patricia Román-Carrasco ◽  
Pilar Alberdi ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Developmental Stages ◽  
Toxocara Canis ◽  
Hygiene Hypothesis ◽  
Parasitic Infections ◽  
Parasitic Fungi ◽  
Parasite Infections ◽  
Mammalian Meat ◽  
And Control

α-Gal syndrome (AGS) is a type of anaphylactic reaction to mammalian meat characterized by an immunoglobulin (Ig)E immune response to the oligosaccharide α-Gal (Galα1-3Galβ1-4GlcNAc-R). Tick bites seems to be a prerequisite for the onset of the allergic disease in humans, but the implication of non-tick parasites in α-Gal sensitization has also been deliberated. In the present study, we therefore evaluated the capacity of helminths (Toxocara canis, Ascaris suum, Schistosoma mansoni), protozoa (Toxoplasma gondii), and parasitic fungi (Aspergillus fumigatus) to induce an immune response to α-Gal. For this, different developmental stages of the infectious agents were tested for the presence of α-Gal. Next, the potential correlation between immune responses to α-Gal and the parasite infections was investigated by testing sera collected from patients with AGS and those infected with the parasites. Our results showed that S. mansoni and A. fumigatus produce the terminal α-Gal moieties, but they were not able to induce the production of specific antibodies. By contrast, T. canis, A. suum and T. gondii lack the α-Gal epitope. Furthermore, the patients with T. canis infection had significantly decreased anti-α-Gal IgE levels when compared to the healthy controls, suggesting the potential role of this nematode parasite in suppressing the allergic response to the glycan molecule. This rather intriguing observation is discussed in the context of the ‘hygiene hypothesis’. Taken together, our study provides new insights into the relationships between immune responses to α-Gal and parasitic infections. However, further investigations should be undertaken to identify T. canis components with potent immunomodulatory properties and to assess their potential to be used in immunotherapy and control of AGS.

scholarly journals Role of Common γ-Chain Cytokines in Lung Interleukin-22 Regulation after Acute Exposure to Aspergillus fumigatus

2018 ◽  
Vol 86 (10) ◽  
Author(s):  
Kristen M. Reeder ◽  
Joseph J. Mackel ◽  
Matthew S. Godwin ◽  
Chad W. Dunaway ◽  
Jonathan P. Blackburn ◽  
...  
Keyword(s):  
T Cells ◽  
Aspergillus Fumigatus ◽  
Γδ T Cells ◽  
Protective Role ◽  
Lymphoid Cells ◽  
Inkt Cells ◽  
Content Type ◽  
Interleukin 22 ◽  
Cell Sources

ABSTRACT Humans are constantly exposed to the opportunistic mold Aspergillus fumigatus, and disease caused by this pathogen is often determined by the magnitude of local and systemic immune responses. We have previously shown a protective role for interleukin-22 (IL-22) after acute A. fumigatus exposure. Here, employing IL-22Cre R26ReYFP reporter mice, we identified iNKT cells, γδ T cells, and type 3 innate lymphoid cells (ILC3s) as lung cell sources of IL-22 in response to acute A. fumigatus exposure. As these cells often utilize common γ-chain cytokines for their development or maintenance, we determined the role of IL-7, IL-21, and IL-15 in lung IL-22 induction and A. fumigatus lung clearance. We observed that IL-7, IL-21, and IL-15 were essential for, partially required for, or negatively regulated the production of IL-22, respectively. Deficiency in IL-7 and IL-21, but not IL-15R, resulted in impaired fungal clearance. Surprisingly, however, the absence of IL-7, IL-21, or IL-15R signaling had no effect on neutrophil recruitment. The levels of IL-1α, an essential anti-A. fumigatus proinflammatory cytokine, were increased in the absence of IL-7 and IL-15R but decreased in the absence of IL-21. IL-7 was responsible for maintaining lung iNKT cells and γδ T cells, whereas IL-21 was responsible for maintaining lung iNKT cells and ILC3s. In contrast, IL-15R deficiency had no effect on the absolute numbers of any IL-22 cell source, rather resulting in enhanced per cell production of IL-22 by iNKT cells and γδ T cells. Collectively, these results provide insight into how the IL-22 response in the lung is shaped after acute A. fumigatus exposure.

scholarly journals Transcription factor Bcl11b sustains iNKT1 and iNKT2 cell programs, restricts iNKT17 cell program, and governs iNKT cell survival

2016 ◽  
Vol 113 (27) ◽  
pp. 7608-7613 ◽  
Author(s):  
Mohammad Nizam Uddin ◽  
Dil Afroz Sultana ◽  
Kyle J. Lorentsen ◽  
Jonathan J. Cho ◽  
Mariana E. Kirst ◽  
...  
Keyword(s):  
T Cells ◽  
Transcription Factor ◽  
Immune Responses ◽  
Cytokine Production ◽  
Inkt Cells ◽  
Double Positive ◽  
Cell Numbers ◽  
Function Identity ◽  
Invariant Natural Killer

Invariant natural killer T (iNKT) cells are innate-like T cells that recognize glycolipid antigens and play critical roles in regulation of immune responses. Based on expression of the transcription factors (TFs) Tbet, Plzf, and Rorγt, iNKT cells have been classified in effector subsets that emerge in the thymus, namely, iNKT1, iNKT2, and iNKT17. Deficiency in the TF Bcl11b in double-positive (DP) thymocytes has been shown to cause absence of iNKT cells in the thymus and periphery due to defective self glycolipid processing and presentation by DP thymocytes and undefined intrinsic alterations in iNKT precursors. We used a model of cre-mediated postselection deletion of Bcl11b in iNKT cells to determine its intrinsic role in these cells. We found that Bcl11b is expressed equivalently in all three effector iNKT subsets, and its removal caused a reduction in the numbers of iNKT1 and iNKT2 cells, but not in the numbers of iNKT17 cells. Additionally, we show that Bcl11b sustains subset-specific cytokine production by iNKT1 and iNKT2 cells and restricts expression of iNKT17 genes in iNKT1 and iNKT2 subsets, overall restraining the iNKT17 program in iNKT cells. The total numbers of iNKT cells were reduced in the absence of Bcl11b both in the thymus and periphery, associated with the decrease in iNKT1 and iNKT2 cell numbers and decrease in survival, related to changes in survival/apoptosis genes. Thus, these results extend our understanding of the role of Bcl11b in iNKT cells beyond their selection and demonstrate that Bcl11b is a key regulator of iNKT effector subsets, their function, identity, and survival.

scholarly journals Tissue-Resident Lymphocytes: Implications in Immunotherapy for Hepatocellular Carcinoma

2020 ◽  
Vol 22 (1) ◽  
pp. 232
Author(s):  
Ji Won Han ◽  
Seung Kew Yoon
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Population ◽  
Tumor Immunity ◽  
Checkpoint Inhibitors ◽  
Γδ T Cells ◽  
Treg Cells ◽  
Inkt Cells ◽  
Mait Cells ◽  
Invariant Natural Killer

Hepatocellular carcinoma (HCC) is a hard-to-treat cancer. The recent introduction of immune checkpoint inhibitors (ICIs) provided viable options to treat HCC, but the response rate is currently not sufficient. Thus, a better understanding of ICI-responding cells within tumors is needed to improve outcomes of ICI treatment in HCC. Recently, tissue-resident memory T (TRM) cells were defined as a subset of the memory T cell population; this cell population is actively under investigation to elucidate its role in anti-tumor immunity. In addition, the role of other tissue-resident populations such as tissue resident regulatory T (Treg) cells, mucosal associated invariant T (MAIT) cells, γδ T cells, and invariant natural killer T (iNKT) cells in anti-tumor immunity is also actively being investigated. However, there is no study that summarizes recent studies and discusses future perspectives in terms of tissue resident lymphocytes in HCC. In this review, we summarize key features of tissue-resident lymphocytes and their role in the anti-tumor immunity. Additionally, we review recent studies regarding the characteristics of tissue-resident lymphocytes in HCC and their role in ICI treatment and other immunotherapeutic strategies.

scholarly journals CD1d-Dependent iNKT Cells Control DSS-Induced Colitis in a Mouse Model of IFNγ-Mediated Hyperinflammation by Increasing IL22-Secreting ILC3 Cells

2021 ◽  
Vol 22 (3) ◽  
pp. 1250
Author(s):  
Hyun Jung Park ◽  
Sung Won Lee ◽  
Luc Van Kaer ◽  
Seokmann Hong
Keyword(s):  
Intestinal Inflammation ◽  
Critical Role ◽  
Lymphoid Cells ◽  
Inkt Cell ◽  
Mesenteric Lymph Nodes ◽  
Inkt Cells ◽  
Mesenteric Lymph ◽  
Type 3

We have previously shown that CD1d-restricted iNKT cells suppress dysregulated IFNγ expression and intestinal inflammation in Yeti mice on the C57BL/6 background. Since type 3 innate lymphoid cells (ILC3s) in mesenteric lymph nodes (MLN) protect against intestinal inflammation in a CD1d-associated manner, we investigated whether crosstalk between iNKT cells and MLN ILC3s controls IFNγ-mediated intestinal inflammation in Yeti mice. We found that Yeti mice display increased levels of ILC3s and that iNKT cell deficiency in Yeti/CD1d KO mice decreases levels of IL22-producing ILC3s during DSS-induced colitis. This finding indicates that iNKT cells and ILC3s cooperate to regulate intestinal inflammation in Yeti mice. Yeti iNKT cells displayed a pronounced anti-inflammatory (IL4- or IL9-producing) phenotype during colitis. Their adoptive transfer to iNKT cell-deficient animals induced a significant increase in IL22 production by ILC3s, indicating that crosstalk between iNKT cells and ILC3s plays a critical role in modulating colitis in Yeti mice. Moreover, we showed that the IL9-producing subset of iNKT cells potently enhances IL22-producing ILC3s in vivo. Taken together, our results identify a central role of the iNKT cell-ILC3 axis in ameliorating IFNγ-mediated intestinal inflammation.

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