Photochemotherapy Induces Interferon Type III Expression via STING Pathway
DNA-damaging cancer therapies induce interferon expression and stimulate the immune system, promoting therapy responses. The immune-activating STING (Stimulator of Interferon Genes) pathway is induced when DNA or double-stranded RNA (dsRNA) is detected in the cell cytoplasm, which can be caused by v...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-11-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/11/2452 |
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| author | Edyta Biskup Brian Daniel Larsen Leonor Rib Lasse Folkersen Omid Niazi Maria R. Kamstrup Claus Storgaard Sørensen |
| author_facet | Edyta Biskup Brian Daniel Larsen Leonor Rib Lasse Folkersen Omid Niazi Maria R. Kamstrup Claus Storgaard Sørensen |
| author_sort | Edyta Biskup |
| collection | DOAJ |
| description | DNA-damaging cancer therapies induce interferon expression and stimulate the immune system, promoting therapy responses. The immune-activating STING (Stimulator of Interferon Genes) pathway is induced when DNA or double-stranded RNA (dsRNA) is detected in the cell cytoplasm, which can be caused by viral infection or by DNA damage following chemo- or radiotherapy. Here, we investigated the responses of cutaneous T-cell lymphoma (CTCL) cells to the clinically applied DNA crosslinking photochemotherapy (combination of 8–methoxypsoralen and UVA light; 8–MOP + UVA). We showed that this treatment evokes interferon expression and that the type III interferon IFNL1 is the major cytokine induced. IFNL1 upregulation is dependent on STING and on the cytoplasmic DNA sensor cyclic GMP-AMP synthase (cGAS). Furthermore, 8–MOP + UVA treatment induced the expression of genes in pathways involved in response to the tumor necrosis factor, innate immune system and acute inflammatory response. Notably, a subset of these genes was under control of the STING–IFNL1 pathway. In conclusion, our data connected DNA damage with immune system activation via the STING pathway and contributed to a better understanding of the effectiveness of photochemotherapy. |
| first_indexed | 2024-03-10T14:57:55Z |
| format | Article |
| id | doaj.art-76757f2848744b5f82efde858e5b6142 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T14:57:55Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-76757f2848744b5f82efde858e5b61422023-11-20T20:26:56ZengMDPI AGCells2073-44092020-11-01911245210.3390/cells9112452Photochemotherapy Induces Interferon Type III Expression via STING PathwayEdyta Biskup0Brian Daniel Larsen1Leonor Rib2Lasse Folkersen3Omid Niazi4Maria R. Kamstrup5Claus Storgaard Sørensen6Department of Dermatology, Bispebjerg Hospital, DK-1014 Copenhagen, DenmarkBiotech Research and Innovation Centre, University of Copenhagen, DK-1014 Copenhagen, DenmarkBiotech Research and Innovation Centre, University of Copenhagen, DK-1014 Copenhagen, DenmarkNational Genome Center Denmark, Department of Bioinformatics, DK-1014 Copenhagen, DenmarkDepartment of Dermatology, Bispebjerg Hospital, DK-1014 Copenhagen, DenmarkDepartment of Dermatology, Bispebjerg Hospital, DK-1014 Copenhagen, DenmarkBiotech Research and Innovation Centre, University of Copenhagen, DK-1014 Copenhagen, DenmarkDNA-damaging cancer therapies induce interferon expression and stimulate the immune system, promoting therapy responses. The immune-activating STING (Stimulator of Interferon Genes) pathway is induced when DNA or double-stranded RNA (dsRNA) is detected in the cell cytoplasm, which can be caused by viral infection or by DNA damage following chemo- or radiotherapy. Here, we investigated the responses of cutaneous T-cell lymphoma (CTCL) cells to the clinically applied DNA crosslinking photochemotherapy (combination of 8–methoxypsoralen and UVA light; 8–MOP + UVA). We showed that this treatment evokes interferon expression and that the type III interferon IFNL1 is the major cytokine induced. IFNL1 upregulation is dependent on STING and on the cytoplasmic DNA sensor cyclic GMP-AMP synthase (cGAS). Furthermore, 8–MOP + UVA treatment induced the expression of genes in pathways involved in response to the tumor necrosis factor, innate immune system and acute inflammatory response. Notably, a subset of these genes was under control of the STING–IFNL1 pathway. In conclusion, our data connected DNA damage with immune system activation via the STING pathway and contributed to a better understanding of the effectiveness of photochemotherapy.https://www.mdpi.com/2073-4409/9/11/2452DNA damageSTINGPUVACTCLIFNL1 |
| spellingShingle | Edyta Biskup Brian Daniel Larsen Leonor Rib Lasse Folkersen Omid Niazi Maria R. Kamstrup Claus Storgaard Sørensen Photochemotherapy Induces Interferon Type III Expression via STING Pathway Cells DNA damage STING PUVA CTCL IFNL1 |
| title | Photochemotherapy Induces Interferon Type III Expression via STING Pathway |
| title_full | Photochemotherapy Induces Interferon Type III Expression via STING Pathway |
| title_fullStr | Photochemotherapy Induces Interferon Type III Expression via STING Pathway |
| title_full_unstemmed | Photochemotherapy Induces Interferon Type III Expression via STING Pathway |
| title_short | Photochemotherapy Induces Interferon Type III Expression via STING Pathway |
| title_sort | photochemotherapy induces interferon type iii expression via sting pathway |
| topic | DNA damage STING PUVA CTCL IFNL1 |
| url | https://www.mdpi.com/2073-4409/9/11/2452 |
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