IFITM3 restricts virus-induced inflammatory cytokine production by limiting Nogo-B mediated TLR responses
Interferon-induced transmembrane protein 3 (IFITM3) is a restriction factor that limits viral pathogenesis and exerts poorly understood immunoregulatory functions. Here, using human and mouse models, we demonstrate that IFITM3 promotes MyD88-dependent, TLR-mediated IL-6 production following exposure...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Springer Nature
2022
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| _version_ | 1826308957560373248 |
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| author | Clement, M Forbester, JL Marsden, M Sabberwal, P Sommerville, MS Wellington, D Dimonte, S Clare, S Harcourt, K Yin, Z Nobre, L Antrobus, R Jin, B Chen, M Makvandi-Nejad, S Lindborg, JA Strittmatter, SM Weekes, MP Stanton, RJ Dong, T Humphreys, IR |
| author_facet | Clement, M Forbester, JL Marsden, M Sabberwal, P Sommerville, MS Wellington, D Dimonte, S Clare, S Harcourt, K Yin, Z Nobre, L Antrobus, R Jin, B Chen, M Makvandi-Nejad, S Lindborg, JA Strittmatter, SM Weekes, MP Stanton, RJ Dong, T Humphreys, IR |
| author_sort | Clement, M |
| collection | OXFORD |
| description | Interferon-induced transmembrane protein 3 (IFITM3) is a restriction factor that limits viral pathogenesis and exerts poorly understood immunoregulatory functions. Here, using human and mouse models, we demonstrate that IFITM3 promotes MyD88-dependent, TLR-mediated IL-6 production following exposure to cytomegalovirus (CMV). IFITM3 also restricts IL-6 production in response to influenza and SARS-CoV-2. In dendritic cells, IFITM3 binds to the reticulon 4 isoform Nogo-B and promotes its proteasomal degradation. We reveal that Nogo-B mediates TLR-dependent pro-inflammatory cytokine production and promotes viral pathogenesis in vivo, and in the case of TLR2 responses, this process involves alteration of TLR2 cellular localization. Nogo-B deletion abrogates inflammatory cytokine responses and associated disease in virus-infected IFITM3-deficient mice. Thus, we uncover Nogo-B as a driver of viral pathogenesis and highlight an immunoregulatory pathway in which IFITM3 fine-tunes the responsiveness of myeloid cells to viral stimulation. |
| first_indexed | 2024-03-07T07:27:05Z |
| format | Journal article |
| id | oxford-uuid:3f520dc6-e3c4-4e84-870a-e3d579ec8914 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:27:05Z |
| publishDate | 2022 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:3f520dc6-e3c4-4e84-870a-e3d579ec89142022-11-28T15:22:59ZIFITM3 restricts virus-induced inflammatory cytokine production by limiting Nogo-B mediated TLR responsesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3f520dc6-e3c4-4e84-870a-e3d579ec8914EnglishSymplectic ElementsSpringer Nature2022Clement, MForbester, JLMarsden, MSabberwal, PSommerville, MSWellington, DDimonte, SClare, SHarcourt, KYin, ZNobre, LAntrobus, RJin, BChen, MMakvandi-Nejad, SLindborg, JAStrittmatter, SMWeekes, MPStanton, RJDong, THumphreys, IRInterferon-induced transmembrane protein 3 (IFITM3) is a restriction factor that limits viral pathogenesis and exerts poorly understood immunoregulatory functions. Here, using human and mouse models, we demonstrate that IFITM3 promotes MyD88-dependent, TLR-mediated IL-6 production following exposure to cytomegalovirus (CMV). IFITM3 also restricts IL-6 production in response to influenza and SARS-CoV-2. In dendritic cells, IFITM3 binds to the reticulon 4 isoform Nogo-B and promotes its proteasomal degradation. We reveal that Nogo-B mediates TLR-dependent pro-inflammatory cytokine production and promotes viral pathogenesis in vivo, and in the case of TLR2 responses, this process involves alteration of TLR2 cellular localization. Nogo-B deletion abrogates inflammatory cytokine responses and associated disease in virus-infected IFITM3-deficient mice. Thus, we uncover Nogo-B as a driver of viral pathogenesis and highlight an immunoregulatory pathway in which IFITM3 fine-tunes the responsiveness of myeloid cells to viral stimulation. |
| spellingShingle | Clement, M Forbester, JL Marsden, M Sabberwal, P Sommerville, MS Wellington, D Dimonte, S Clare, S Harcourt, K Yin, Z Nobre, L Antrobus, R Jin, B Chen, M Makvandi-Nejad, S Lindborg, JA Strittmatter, SM Weekes, MP Stanton, RJ Dong, T Humphreys, IR IFITM3 restricts virus-induced inflammatory cytokine production by limiting Nogo-B mediated TLR responses |
| title | IFITM3 restricts virus-induced inflammatory cytokine production by limiting Nogo-B mediated TLR responses |
| title_full | IFITM3 restricts virus-induced inflammatory cytokine production by limiting Nogo-B mediated TLR responses |
| title_fullStr | IFITM3 restricts virus-induced inflammatory cytokine production by limiting Nogo-B mediated TLR responses |
| title_full_unstemmed | IFITM3 restricts virus-induced inflammatory cytokine production by limiting Nogo-B mediated TLR responses |
| title_short | IFITM3 restricts virus-induced inflammatory cytokine production by limiting Nogo-B mediated TLR responses |
| title_sort | ifitm3 restricts virus induced inflammatory cytokine production by limiting nogo b mediated tlr responses |
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