Modeling the Effect of the Aryl Hydrocarbon Receptor on Transplant Immunity
| Autor: | John H. Fechner, Amanda Mueller, Leah A. Owens, Jeremy A. Sullivan, Joshua D. Mezrich, Ling Zhou, Walker Julliard, Lynn Frydrych, Chelsea A. O’Driscoll |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Transplantation biology Inhalation business.industry T cell T helper cell 030230 surgery Aryl hydrocarbon receptor 3. Good health Histocompatibility 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Immune system Basic Science Antigen 13. Climate action Immunity Immunology biology.protein medicine business |
| Zdroj: | Transplantation Direct |
| ISSN: | 2373-8731 |
| DOI: | 10.1097/txd.0000000000000666 |
| Popis: | Background Exposure to pollutants through inhalation is a risk factor for lung diseases including cancer, asthma, and lung transplant rejection, but knowledge of the effects of inhaled pollutants on pathologies outside of the lung is limited. Methods Using the minor-mismatched model of male C57BL/6J (B6) to female B6 skin grafts, recipient mice were treated with an inhaled urban dust particle sample every 3 days before and after grafting. Graft survival time was determined, and analysis of the resulting immune response was performed at time before rejection. Results Significant prolongation of male skin grafts occurred in recipient female mice treated with urban dust particles compared with controls and was found to be dependent on aryl hydrocarbon receptor (AHR) expression in the recipient mouse. T cell responses to the male histocompatibility antigen (H-Y) Dby were not altered by exposure to pollutants. A reduction in the frequency of IFNγ-producing CD4 T cells infiltrating the graft on day 7 posttransplant was observed. Flow cytometry analysis revealed that AHR expression is upregulated in IFNγ-producing CD4 T cells during immune responses in vitro and in vivo. Conclusions Surprisingly, inhalation of a pollutant standard was found to prolong graft survival in a minor-mismatched skin graft model in an AHR-dependent manner. One possible mechanism may be an effect on IFNγ-producing CD4 T cells responding to donor antigen. The increased expression of AHR in this CD4 T cell subset suggests that AHR ligands within the particulate matter may be directly affecting the type 1 T helper cell response in this model. |
| Databáze: | OpenAIRE |
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