scholarly journals Single-cell transcriptomics of the naked mole-rat reveals unexpected features of mammalian immunity

2019 ◽  
Author(s):  
HG Hilton ◽  
ND Rubinstein ◽  
P Janki ◽  
AT Ireland ◽  
N Bernstein ◽  
...  

AbstractUsing single-cell transcriptional profiling we mapped the immune system of the naked mole-rat (Heterocephalus glaber), a small but long-lived and cancer-resistant subterranean rodent. Both splenic and circulating immune cells were examined in healthy young animals and following an infection-mimicking lipopolysaccharide challenge. Our study revealed that the naked mole-rat immune system is characterized by a high myeloid to lymphoid cell ratio that includes a novel, lipopolysaccharide responsive, granulocyte cell subset not found in the mouse. Conversely, we find that naked mole-rats do not have a cell subset that corresponds to natural killer cells as defined in other well-characterized mammalian species. Supporting this finding, we show that the naked mole-rat genome has not expanded any of the gene families encoding diverse natural killer cell receptors, which are the genomic hallmarks of species in which natural killer cells have been described. These unusual features suggest an atypical mode of immunosurveillance and a greater reliance on myeloid-biased innate immunity.

2003 ◽  
Vol 198 (8) ◽  
pp. 1201-1212 ◽  
Author(s):  
Louise A. Koopman ◽  
Hernan D. Kopcow ◽  
Basya Rybalov ◽  
Jonathan E. Boyson ◽  
Jordan S. Orange ◽  
...  

Natural killer cells constitute 50–90% of lymphocytes in human uterine decidua in early pregnancy. Here, CD56bright uterine decidual NK (dNK) cells were compared with the CD56bright and CD56dim peripheral NK cell subsets by microarray analysis, with verification of results by flow cytometry and RT-PCR. Among the ∼10,000 genes studied, 278 genes showed at least a threefold change with P ≤ 0.001 when comparing the dNK and peripheral NK cell subsets, most displaying increased expression in dNK cells. The largest number of these encoded surface proteins, including the unusual lectinlike receptors NKG2E and Ly-49L, several killer cell Ig-like receptors, the integrin subunits αD, αX, β1, and β5, and multiple tetraspanins (CD9, CD151, CD53, CD63, and TSPAN-5). Additionally, two secreted proteins, galectin-1 and progestagen-associated protein 14, known to have immunomodulatory functions, were selectively expressed in dNK cells.


2020 ◽  
Vol 21 (12) ◽  
pp. 1176-1185 ◽  
Author(s):  
Tuğcan Korak ◽  
Emel Ergül ◽  
Ali Sazci

Background: In the last decade, there have been accumulating data that the use of medicinal plants could bring additional benefits to the supportive treatment of various diseases. Nigella sativa (N. sativa, family Ranunculaceae) is one of these plants that has attracted considerable interest. The extracts and seeds of N. sativa and its active component thymoquinone have been studied extensively and the results suggest that N. sativa might carry some therapeutic potential for many diseases, including cancer. Methods: The selection criteria for references were applied through Pubmed with “N. sativa and cancer”, “N. sativa and breast cancer”, “N. sativa and metastasis”, “N. sativa and cytotoxicity of natural killer cells”. The pathway analysis was performed using the PANTHER tool by using five randomly selected N. sativa affected genes (Cyclin D1, P53, p21 protein (Cdc42/Rac) activated kinase 1 (PAK1), B-cell lymphoma 2 (Bcl-2) and vascular endothelial growth factor (VEGF)) in order to elucidate further potentially affected signaling pathways. Results: The aim of this review was to summarize studies regarding the effects of N. sativa in cancer generally, with a focus on breast cancer, its anti-metastatic effects, and how N. sativa modulates the cytotoxicity of Natural Killer cells that play a crucial role in tumor surveillance. Conclusion: In summary, the data suggest that N. sativa might be used for its anti-cancer and antimetastatic properties and as an immune system activator against cancer.


2014 ◽  
Vol 31 (3) ◽  
pp. 157-164 ◽  
Author(s):  
Casimir de Rham ◽  
Karine Hadaya ◽  
Cédric Bandelier ◽  
Sylvie Ferrari-Lacraz ◽  
Jean Villard

2000 ◽  
Vol 99 (1) ◽  
pp. 9-17 ◽  
Author(s):  
Christopher A. O'CALLAGHAN

HLA-E (human leucocyte antigen-E) is a conserved class I major histocompatibility molecule which has only limited polymorphism. It binds to the leader peptide derived from the polymorphic classical major histocompatibility molecules HLA-A, HLA-B and HLA-C. This peptide binding is highly specific and stabilizes the HLA-E protein, allowing it to migrate to the cell surface. A functioning TAP (transporter associated with antigen processing) molecule is required to transport these peptides into the endoplasmic reticulum, where they can interact with HLA-E. HLA-E then migrates to the cell surface, where it interacts with CD94/NKG2A receptors on natural killer cells. This interaction inhibits natural killer cell-mediated lysis of a cell displaying HLA-E. If the leader peptide is not present in the endoplasmic reticulum, HLA-E is unstable and is degraded before it reaches the cell surface. In damaged cells, such as virally infected or tumour cells, down-regulation of HLA-A, HLA-B and HLA-C production or inhibition of TAP prevents stabilization of HLA-E by the leader peptide. Under these circumstances, HLA-E does not reach the cell surface and the cell is then vulnerable to lysis by natural killer cells. The molecular mechanisms underlying this function of HLA-E have been revealed by crystallographic studies of the structure of HLA-E.


Immunology ◽  
2017 ◽  
Vol 151 (1) ◽  
pp. 89-97 ◽  
Author(s):  
Carly A. Hamilton ◽  
Suman Mahan ◽  
Charlotte R. Bell ◽  
Bernardo Villarreal-Ramos ◽  
Bryan Charleston ◽  
...  

1990 ◽  
Vol 4 (7) ◽  
pp. 303-308 ◽  
Author(s):  
F Hadziselimovic ◽  
LR Emmons ◽  
U Schaub

The occurrence of natural killer cells and large granular lymphocytes (LGL) within the epithelium of colonic mucosa in children with inflammatory bowel disease (IBD) was compared to normal controls. Their numbers and localization within the epithelium from various regions of the colon were analyzed with immunohistochemical techniques using fluorescent, light and electron microscopy. The average number of natural killer cells and LGL in normal controls was 3.0±1.l per mn2. In contrast, there were no natural killer cells in the gut epithelium of children with IBD, irrespective of disease activity, whether the biopsy specimens were obtained from involved or uninvolved inflammatory regions of the gut, or the treatment status of the patients. However, the number of natural killer cells was normal in patients in remission with left-sided colitis. The lack of natural killer cells and LGL in the gut epithelium in children with IBD may be indicative of a possible genetic predisposition. The authors also present a new therapeutic strategy consisting of low dose interferon-alpha-2a that is efficacious in ameliorating ulcerative col iris and Crohn's disease and concomitantly increasing the number of natural killer cells and LGL in the gut.


Sign in / Sign up

Export Citation Format

Share Document