Aquaporin-9-expressing neutrophils are required for the establishment of contact hypersensitivity

Catharina Sagita Moniaga, Sachiko Watanabe, Tetsuya Honda, Søren Nielsen, Mariko Hara-Chikuma

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36 Citations (Scopus)


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.

Original languageEnglish
Article number15319
JournalScientific reports
Publication statusPublished - 2015 Oct 22
Externally publishedYes

ASJC Scopus subject areas

  • General


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