Abstract
Aquaporin-9 (AQP9), a water/glycerol channel protein, is expressed in several immune cells including neutrophils; however, its role in immune response remains unknown. Here we show the involvement of AQP9 in hapten-induced contact hypersensitivity (CHS), as a murine model of skin allergic contact dermatitis, using AQP9 knockout (AQP9−/−) mice. First, the CHS response to hapten dinitrofluorobenzene (DNFB) was impaired in AQP9−/− mice compared with wild-type (WT) mice. Adoptive transfer of sensitized AQP9−/− draining lymph node (dLN) cells into WT recipients resulted in a reduced CHS response, indicating impaired sensitization in AQP9−/− mice. Second, administration of WT neutrophils into AQP9−/− mice during sensitization rescued the impaired CHS response. Neutrophil recruitment to dLNs upon hapten application was attenuated by AQP9 deficiency. Coincidentally, AQP9−/− neutrophils showed a reduced CC-chemokine receptor 7 (CCR7) ligand-induced migration efficacy, which was attributed to the attenuated recruitment of neutrophils to dLNs. Furthermore, we found that neutrophil deficiency, observed in AQP9−/− or neutrophil-depleted mice, decreased IL-17A production by dLN cells, which might be responsible for T cell activation during a subsequent CHS response. Taken together, these findings suggest that AQP9 is required for the development of sensitization during cutaneous acquired immune responses via regulating neutrophil function.
Highlights
Allergic contact dermatitis (ACD) is one of the most prevalent skin diseases consisting of sensitization and elicitation phases[1,2]
The cell numbers in skin draining lymph nodes (dLNs), bone marrow (BM), and blood were comparable between WT and AQP9−/− mice (Fig. 1F)
The adoptive transfer of AQP9−/− dLN cells with DNFB application to the site of the secondary challenge impaired the contact hypersensitivity (CHS) response, indicating that the development of sensitization was impaired in AQP9−/− mice
Summary
Allergic contact dermatitis (ACD) is one of the most prevalent skin diseases consisting of sensitization and elicitation phases[1,2]. Advanced studies of hapten-induced contact hypersensitivity (CHS) as a murine model of ACD have expanded our understanding of the mechanism of allergic reactions occurring in the skin, especially the specific roles of a variety of immune cells. Increasing evidence shows that several subsets of immune cells, including various types of T cells (Th1, Th17, regulatory, and natural killer), DCs (dermal DCs and Langerhans cells), and mast cells, work synergistically in the skin and its dLNs to exert antigen presentation and T cell activation during the development of sensitization in CHS3–7. Our study using AQP9−/− mice and a CHS murine model has shown that AQP9-expressing neutrophils is required for the sensitization phase of CHS through the cell migration function
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
