Cutting Edge: Role of NK Cells and Surfactant Protein D in Dendritic Cell Lymph Node Homing: Effects of Ozone Exposure

Abstract

The role of natural killer (NK) cells, surfactant protein D (SP-D), IFN-γ and the effect of ozone (O3) inhalation was studied on recirculation of pulmonary dendritic cells (DC) to the mediastinal lymph nodes. Both O3 exposure and lack of SP-D reduced NK cell IFN-γ and lung tissue CCL21 mRNA expression and impaired DC homing to the mediastinal lymph nodes. Notably, addition of recombinant SP-D to naïve mononuclear cells stimulated IFN-γ release in vitro. Because NKp46, a glycosylated membrane receptor, was necessary for dose-dependent SP-D binding to NK cells in vitro and DC migration in vivo, we speculate that SP-D may constitutively stimulate IFN-γ production by NK cells possibly via NKp46. This mechanism could then initiate the IFN-γ/IL-12 feedback circuit, a key amplifier of DC lymph node homing. Inhibition of this process during an acute inflammatory response causes DC retention in the peripheral lung tissue and contributes to injury.

Oxidative damage of SP-D abolishes control of eosinophil extracellular DNA trap formation

“…Our laboratory and others previously showed that SP‐D deficiency predisposes to inflammation of the airways and lung parenchyma leading to chronic disease . Although the role of SP‐D in modulating macrophage and dendritic cell function for host defense has been well documented, its regulatory function in allergic airways inflammation and especially on eosinophil activation has been unclear.…”

“…SP‐D induction was mediated by IL‐6 in type II alveolar epithelial cells . We also showed that SP‐D can directly bind to immune cells of the lung thereby regulating pulmonary immune homeostasis during the inflammatory response.…”

Ozone-induced enhancement of airway hyperreactivity in rhesus macaques: Effects of antioxidant treatment

“…8,51 Previously, we showed that oxidative damage to the quaternary structure of SP-D 9 or genetic deficiency of the SP-D gene (SFPTD) conveys heightened susceptibility to inflammatory changes. 5,7 IL-6, a cytokine essential in eliciting neutrophilia and AHR in response to O 3 , is also important for inducing SP-D mRNA activation. 7,52 In the macaque airway epithelium, O 3 induced both the IL6 and SFPTD genes, and this effect was reversed by LGM2605.…”

“…Although it is not known how exactly DCs can regulate the inflammatory airway response, different DC subsets have specific functions (see Fig E7 in this article's Online Repository at www.jacionline.org). 5 We studied the myeloid CD1 1 and CD16 1 and the plasmacytoid CD123 1 DC populations. We found the most striking changes in absolute BAL fluid counts of CD1c 1 myeloid dendritic cells (mDCs) and CD123 1 plasmacytoid dendritic cells (pDCs) in response to O 3 (Fig 4, A), whereas there were no significant changes in CD16 1 mDC counts from day 1 to day 8 (data not shown).…”

“…Using mice, our laboratory previously showed that airway epithelial cells, dendritic cells (DCs), natural killer cells, 5 and group 2 innate lymphoid cells (ILC2s) 6 play highly proinflammatory roles, whereas the presence of the immunoprotective surfactant protein D (SP-D), an epithelium-derived lung collectin, is important in attenuating the O 3 -induced inflammatory process. [5][6][7][8][9] Establishment of the clinical relevance of these findings has been hindered because of the lack of adequate experimental systems.…”