Aquaporin-9-expressing neutrophils are required for the establishment of contact hypersensitivity.
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.
Center for Innovation in Immunoregulative Technology and Therapeutics.
Catharina Sagita
CS
Moniaga
Center for Innovation in Immunoregulative Technology and Therapeutics.
Sachiko
S
Watanabe
Center for Innovation in Immunoregulative Technology and Therapeutics.|Department of Dermatology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Tetsuya
T
Honda
Department of Health Science and Technology, Aalborg University, Aalborg 9220, Denmark.
Søren
S
Nielsen
Center for Innovation in Immunoregulative Technology and Therapeutics.
Mariko
M
Hara-Chikuma
D000818:Animals; D020346:Aquaporins / Q000235:genetics*; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D003877:Dermatitis, Contact / Q000235:genetics* / Q000276:immunology; D004139:Dinitrofluorobenzene / Q000008:administration & dosage; D007111:Immunity, Cellular / Q000187:drug effects / Q000235:genetics*; D008024:Ligands; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D054400:Receptors, CCR7 / Q000235:genetics; D012867:Skin / Q000187:drug effects / Q000276:immunology
C491638:Aqp9 protein, mouse; D020346:Aquaporins; C515371:Ccr7 protein, mouse; D008024:Ligands; D054400:Receptors, CCR7; D004139:Dinitrofluorobenzene