The role of Natural Killer cells in allergic airway inflammation

Natural Killer (NK) cells are innate cells of the immune system and constitute 10% of lung lymphocytes. Increasing evidence implicates a role for innate immunity in the pathogenesis of asthma and although there is evidence of a role for NK cells in the development of allergic inflammation, the mechanisms by which NK cells contribute to allergy is not known. To characterise the NK cell response and determine the phenotype of NK cells in allergic pulmonary inflammation we employed a model in which mice are dosed intranasally 3 times a week for 3 weeks with house dust mite (HDM) extract. Numbers of NK cells in the bronchoalveolar lavage (BAL) increased over the time course of HDM challenge and followed a similar trend to eosinophils and Th2 cells. Airway NK cells were activated and expressed NKG2D and granzyme B. In addition, expression of the NKG2D ligand (MULT-1) was upregulated in the lungs of mice treated with HDM. To determine the importance of the NKG2D receptor in allergic inflammation, the HDM model was tested on NKG2D knock out (KO) mice. There was a dramatic reduction in the extent of the inflammatory response in the absence of this receptor, including a reduction in BAL eosinophilia, Th2 responses and serum IgE. Adoptive transfer of wild type (WT) NK cells into NKG2D KO mice restored allergic inflammatory responses to HDM, whereas transfer of granzyme B-/- NK cells did not, demonstrating the requirement for NK cell expression of NKG2D and granzyme B. Detailed phenotypic analysis of NKp46+ cells in the HDM model showed that NKp46+ cells in BAL and lung consisted of RORγt+ and RORγt- subsets. NKp46+RORγt- cells resembled conventional NK cells as they express NKG2D and granzyme B, however NKp46+RORγt+ had similar phenotype to type-3 innate lymphoid cells (ILC3) cells and produced Th2 cytokines upon HDM challenge. We have shown for the first time that NK cells promote allergic lung inflammation via NKG2D and granzyme B production. We have also described for the first time the presence of NKp46+RORγt+ cells in the airways and lung which identifies potential novel therapeutic targets.Open Acces

Evaluation of antibody titers in COVID-19 patients with cerebral or pulmonary symptoms and mild symptoms

Background and Objectives: This study aimed to compare the production of antibodies in three different groups of patients with COVID-19. These groups included patients with pulmonary and cerebral symptoms, as well as those with mild symptoms. Materials and Methods: Blood samples were collected from 80 patients admitted to COVID-19-specific hospitals. The patients had various forms of SARS-CoV-2 disease, including those with pulmonary symptoms, brain involvement, and those with positive PCR test results but mild symptoms. The enzyme-linked immunosorbent assay (ELISA) technique was used to determine the levels of IgM and IgG antibody titers. Results: The levels of IgM and IgG antibody production differed significantly between groups of patients experiencing pulmonary symptoms and cerebral symptoms, with mild symptom patients also showing differences (P=0.0068), (P=0.0487), (P<0.0001), and (P=0.0120), respectively. Furthermore, there was no significant relationship between IgM antibody secretion and age or pulmonary involvement (P=0.1959). However, there was a direct and significant relationship between age and brain involvement (P=0.0317). Conclusion: The findings of this study revealed that the risk of central nervous system involvement increases with age and that older people have lower antibody levels than younger people. Consequently, strengthening the immune systems of people over the age of 78 during this pandemic through vaccination and nutrition is very effective in reducing mortality in this age group

Evaluation of the Interaction of Curcumin and Nigella Sativa on Brain Antitumor Molecule Using an Equilibrium Dynamics Simulation Tool for Biomedical Applications

Curcumin and nigellin-1.1's atomic interactions on brain antitumor molecule are significant in medical research. For the first time, Molecular dynamic simulations based on Newton's law were utilized to predict the destruction of brain antitumor structure by curcumin and nigellin-1.1 with structure in the current research. To depict the atomic development of curcumin, nigellin-1.1, and brain antitumor molecule, DREIDING and universal force fields are used to model C, H, N, O, and S atoms. We calculate the total energy, center of mass distance, diffusion coefficient, and volume of atomic structures to explain the atomic interaction between these structures. The calculated rates for these physical parameters reveal an attraction force between curcumin and brain antitumor structure, as well as nigellin-1.1 and brain antitumor structure, with COM distances between curcumin and brain antitumor structures varying from 1.16 Å to 1.14 Å after 2 ns, and COM distances between nigellin-1.1 structures varying from 2.01 Å to 1.93 Å after 2 ns. The volume of a brain antitumor increases structurally from 1.33×106 Å3 to 2.24×106 Å3 following atomic contact with curcumin, and increases structurally from 1.33×106 Å3 to 2.83×106 Å3 after atomic interaction with nigellin-1.1, indicating tumor eradication

CD1d-mediated activation of group 3 innate lymphoid cells drives IL-22 production

Innate lymphoid cells (ILCs) are a heterogeneous family of immune cells that play a critical role in a variety of immune processes including host defence against infection, wound healing and tissue repair. Whether these cells are involved in lipid-dependent immunity remains unexplored. Here we show that murine ILCs from a variety of tissues express the lipid-presenting molecule CD1d, with group 3 ILCs (ILC3s) showing the highest level of expression. Within the ILC3 family, natural cytotoxicity triggering receptor (NCR) CCR6+ cells displayed the highest levels of CD1d. Expression of CD1d on ILCs is functionally relevant as ILC3s can acquire lipids in vitro and in vivo and load lipids on CD1d to mediate presentation to the T-cell receptor of invariant natural killer T (iNKT) cells. Conversely, engagement of CD1d in vitro and administration of lipid antigen in vivo induce ILC3 activation and production of IL-22. Taken together, our data expose a previously unappreciated role for ILCs in CD1d-mediated immunity, which can modulate tissue homeostasis and inflammatory responses