CXCL16 knockout inhibit asthma airway inflammation by suppressing H2-DM molecular mediated antigen presentation
Abstract The inflammatory microenvironment influences dendritic cell-mediated antigen presentation to regulate asthma Th2 inflammation. The scavenger receptor is expressed on DCs and regulates antigen presentation and T priming. However, whether the transmembrane scavenger receptor (SR-PSOX/CXCL16)...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2025-03-01
|
| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-025-02371-6 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850030074001096704 |
|---|---|
| author | Ting-ting Liu Zhi Zhang Jing Deng Chang-yu Shi Shuai Zheng Li-xin Jia Jie Du Chunmei Piao |
| author_facet | Ting-ting Liu Zhi Zhang Jing Deng Chang-yu Shi Shuai Zheng Li-xin Jia Jie Du Chunmei Piao |
| author_sort | Ting-ting Liu |
| collection | DOAJ |
| description | Abstract The inflammatory microenvironment influences dendritic cell-mediated antigen presentation to regulate asthma Th2 inflammation. The scavenger receptor is expressed on DCs and regulates antigen presentation and T priming. However, whether the transmembrane scavenger receptor (SR-PSOX/CXCL16) regulates the phenotype and antigen presentation function of DCs remains unclear. We found that CXCL16 is mainly expressed on DCs in the lung tissues of asthma patients and asthma mice. CXCL16 knockout led to the suppression of airway inflammation, mucus overproduction, and airway hyperresponsiveness in Aspergillus-induced asthma. In addition, the adoptive transfer of Aspergillus-pulsed DCs shows the CXCL16+ DCs exerted a promoting role in airway inflammation, the CXCL16− DCs inhibit airway inflammation. Additionally, RNA sequencing and flow cytometry data revealed that CXCL16 knockout inhibits airway inflammation by suppressing the antigen processing and presentation function of DCs, which was mediated by MHC II chaperone H2-DM. Furthermore, we found CXCL16 knockout suppressed dendritic cells differentiated forward to cDC2b subtype which is mainly charged with antigen presentation to T cell. In conclusion, we found that CXCL16 downregulated the capacity of DC antigen processing and presentation to suppress airway inflammation by reducing H2-DM expression which mediated DC differentiation. The study suggested that inhibition of CXCL16 can be a potential therapy for asthma. |
| format | Article |
| id | doaj-art-0083005dbee842bc90e90380c88ae2d4 |
| institution | DOAJ |
| issn | 2058-7716 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj-art-0083005dbee842bc90e90380c88ae2d42025-08-20T02:59:19ZengNature Publishing GroupCell Death Discovery2058-77162025-03-0111111210.1038/s41420-025-02371-6CXCL16 knockout inhibit asthma airway inflammation by suppressing H2-DM molecular mediated antigen presentationTing-ting Liu0Zhi Zhang1Jing Deng2Chang-yu Shi3Shuai Zheng4Li-xin Jia5Jie Du6Chunmei Piao7Beijing Anzhen Hospital, Capital Medical UniversityBeijing Institute of Heart, Lung and Blood Vessel DiseasesSchool of Basic Medical Sciences, Yanbian UniversitySchool of Basic Medical Sciences, Yanbian UniversityBeijing Anzhen Hospital, Capital Medical UniversityBeijing Anzhen Hospital, Capital Medical UniversityBeijing Anzhen Hospital, Capital Medical UniversityBeijing Anzhen Hospital, Capital Medical UniversityAbstract The inflammatory microenvironment influences dendritic cell-mediated antigen presentation to regulate asthma Th2 inflammation. The scavenger receptor is expressed on DCs and regulates antigen presentation and T priming. However, whether the transmembrane scavenger receptor (SR-PSOX/CXCL16) regulates the phenotype and antigen presentation function of DCs remains unclear. We found that CXCL16 is mainly expressed on DCs in the lung tissues of asthma patients and asthma mice. CXCL16 knockout led to the suppression of airway inflammation, mucus overproduction, and airway hyperresponsiveness in Aspergillus-induced asthma. In addition, the adoptive transfer of Aspergillus-pulsed DCs shows the CXCL16+ DCs exerted a promoting role in airway inflammation, the CXCL16− DCs inhibit airway inflammation. Additionally, RNA sequencing and flow cytometry data revealed that CXCL16 knockout inhibits airway inflammation by suppressing the antigen processing and presentation function of DCs, which was mediated by MHC II chaperone H2-DM. Furthermore, we found CXCL16 knockout suppressed dendritic cells differentiated forward to cDC2b subtype which is mainly charged with antigen presentation to T cell. In conclusion, we found that CXCL16 downregulated the capacity of DC antigen processing and presentation to suppress airway inflammation by reducing H2-DM expression which mediated DC differentiation. The study suggested that inhibition of CXCL16 can be a potential therapy for asthma.https://doi.org/10.1038/s41420-025-02371-6 |
| spellingShingle | Ting-ting Liu Zhi Zhang Jing Deng Chang-yu Shi Shuai Zheng Li-xin Jia Jie Du Chunmei Piao CXCL16 knockout inhibit asthma airway inflammation by suppressing H2-DM molecular mediated antigen presentation Cell Death Discovery |
| title | CXCL16 knockout inhibit asthma airway inflammation by suppressing H2-DM molecular mediated antigen presentation |
| title_full | CXCL16 knockout inhibit asthma airway inflammation by suppressing H2-DM molecular mediated antigen presentation |
| title_fullStr | CXCL16 knockout inhibit asthma airway inflammation by suppressing H2-DM molecular mediated antigen presentation |
| title_full_unstemmed | CXCL16 knockout inhibit asthma airway inflammation by suppressing H2-DM molecular mediated antigen presentation |
| title_short | CXCL16 knockout inhibit asthma airway inflammation by suppressing H2-DM molecular mediated antigen presentation |
| title_sort | cxcl16 knockout inhibit asthma airway inflammation by suppressing h2 dm molecular mediated antigen presentation |
| url | https://doi.org/10.1038/s41420-025-02371-6 |
| work_keys_str_mv | AT tingtingliu cxcl16knockoutinhibitasthmaairwayinflammationbysuppressingh2dmmolecularmediatedantigenpresentation AT zhizhang cxcl16knockoutinhibitasthmaairwayinflammationbysuppressingh2dmmolecularmediatedantigenpresentation AT jingdeng cxcl16knockoutinhibitasthmaairwayinflammationbysuppressingh2dmmolecularmediatedantigenpresentation AT changyushi cxcl16knockoutinhibitasthmaairwayinflammationbysuppressingh2dmmolecularmediatedantigenpresentation AT shuaizheng cxcl16knockoutinhibitasthmaairwayinflammationbysuppressingh2dmmolecularmediatedantigenpresentation AT lixinjia cxcl16knockoutinhibitasthmaairwayinflammationbysuppressingh2dmmolecularmediatedantigenpresentation AT jiedu cxcl16knockoutinhibitasthmaairwayinflammationbysuppressingh2dmmolecularmediatedantigenpresentation AT chunmeipiao cxcl16knockoutinhibitasthmaairwayinflammationbysuppressingh2dmmolecularmediatedantigenpresentation |