Aquaporin 4 Is A Mediator Of Essential Dendritic Cell Function

Autor: Michael Nicosia, Ashley Beavers, Yosuke Yamamoto, Trevor Thompson, Thomas Zindrick, Anna Valujskikh
Rok vydání: 2022
Předmět:
Zdroj: The Journal of Immunology. 208:102.17-102.17
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.208.supp.102.17
Popis: Aquaporins are transmembrane water channels implicated in a range of physiologic functions. We previously reported that Aquaporin 4 (AQP4) is expressed by T cells and treatment with a small molecule AQP4 inhibitor (AER-270) significantly delays T cell mediated mouse heart allograft rejection. Our findings did not exclude a role for antigen presenting cells (APCs), and the purpose of this study is to investigate the requirement for AQP4 in dendritic cell (DC) functions. Stimulation with AQP4−/− spleen APCs with the addition of antigenic peptide, resulted in reduced frequencies of IFNγ producing MAR T cells compared to WT APCs. We confirmed that splenic DCs express AQP4. Bone marrow derived dendritic cells (BMDCs) from WT and AQP4−/− mice were stimulated with LPS or protein antigen, the absence or inhibition of AQP4 resulted in no defects in up-regulation of maturation markers following stimulation. WT and AQP4−/− BMDCs were pulsed with Lucifer Yellow, FITC-dextran and OVA-AF647 to assess antigen uptake with no observable defect after AQP4 inhibition or in AQP4−/− BMDCs. However, AQP4−/− BMDCs pulsed with OVA protein had reduced expression of SIINFEKL peptide-MHC-I complexes. In contrast, when pulsed with OVA-derived SIINFEKL peptide, AER-270 treated WT BMDCs or AQP4−/− BMDCs showed no change in peptide-MHC complex expression suggesting a role for AQP4 in antigen processing. Consistent with this, the absence or inhibition of AQP4 resulted in decreased DQ-OVA signal, indicating that AQP4 is required for the antigen loading into the lysosome. Our data indicate that AQP4 plays a critical role in the processing of antigens by dendritic cells that impacts their ability to prime T cells, and can be therapeutically targeted in a transplant setting. Supported by grants from NIH (R56AI152368-01)
Databáze: OpenAIRE
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