NKp46 regulates allergic responses

Abstract

Natural killer (NK) cells are cytotoxic cells that are able to rapidly kill viruses, tumor cells, parasites, bacteria, and even cells considered “self”. The activity of NK cells is controlled by a fine balance of inhibitory and activating signals mediated by a complex set of different receptors. However, the function of NK cells is not restricted only to the killing of target cells, NK cells also possess other properties such as the secretion of proangiogenic factors during pregnancy. Here, we demonstrate another unique NK-cell activity, namely the regulation of T-cell mediated allergic responses, which is dependent on the NK-cell specific receptor NKp46 (Ncr1 in mice). Using mice in which the Ncr1 gene has been replaced with a green fluorescent protein, we demonstrate reduced delayed-type hypersensitivity and airway hypersensitivity. Interestingly, we show that this reduction in airway hypersensitivity is due to differences in the stimulation of T cells resulting in an altered cytokine profile.

Role of NKp46 + natural killer cells in house dust mite‐driven asthma

“…Again, the absence of NKp46 + cells did not significantly influence cardinal features of HDM‐driven asthma (Fig C–E), although there was a trend toward lower HDM‐specific IgG1 serum levels in NKp46‐DTA mice. These findings contrast with earlier studies in OVA/alum‐based allergic asthma models (Korsgren et al , ; Ple et al , ; Ghadially et al , ). To exclude allergen‐dependency, littermate and NKp46‐DTA mice were subjected to an OVA/alum‐based allergic asthma model (Fig F and G).…”

“…Initial studies have used NK1.1 or asialo-GM1 (ASGM1) depleting antibodies (Korsgren et al, 1999;Ple et al, 2010), or mice genetically deficient for the activating receptor NKp46 (Ghadially et al, 2013) or NKG2D (Farhadi et al, 2014). These studies showed that NK cells were crucial and non-redundant for asthma development induced by ovalbumin (OVA)/alum (Korsgren et al, 1999;Ple et al, 2010;Ghadially et al, 2013) or chronic HDM exposure (Farhadi et al, 2014). In contrast, increased pulmonary NK cell numbers were recently correlated with reduced HDM-mediated airway inflammation in mice (Ferrini et al, 2016;Simons et al, 2017).…”

Expression of natural cytotoxicity receptors and cytokine production on endometrial natural killer cells in women with recurrent pregnancy loss or implantation failure, and the expression of natural cytotoxicity receptors on peripheral blood natural killer cells in pregnant women with a history of recurrent pregnancy loss

“…A previous study examined the relation between the expression of NCR and cytokines production for decidual NK cells, reporting that NKp46 + decidual NK cells did not have function for cytokine secretion, but that NKp44 + and NKp30 + decidual NK cells did. However, other researchers have reported a relation between low NKp46 expression and decreased production of cytokines, such as IFN‐γ and IL‐13 in allergic responses . Previously, we have also reported the relation between the expression of NKp46 on NK cells and cytokines production by NK cell .…”

Increased NK cell immunity in a transgenic mouse model of NKp46 overexpression

“…They were shown to participate in many immunological and regulatory processes including viral 1–11 , bacterial and fungal infections 12–14 , cancer 8,9,15–20 , graft versus host disease 21 , autoimmunity 22–24 , allergy 25 and pregnancy 26 . NK cells kill their targets when signals from activating and co-activating receptors overcome inhibitory signals 27 .…”