RAB11FIP5-deficient mice exhibit cytokine-related transcriptomic signatures
Rab11 recycling endosomes are involved in immunological synaptic functions, but the roles of Rab11 family-interacting protein 5 (Rab11Fip5), one of the Rab11 effectors, in the immune system remain obscure. Our previous study demonstrated that RAB11FIP5 transcripts are significantly elevated in PBMCs...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
American Association of Immunologists
2020
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| _version_ | 1826305414320357376 |
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| author | Li, D Bradley, T Cain, DW Pedroza-Pacheco, I Aggelakopoulou, M Parks, R Barr, M Xia, S-M Scearce, R Bowman, C Stevens, G Newman, A Hora, B Chen, Y Riebe, K Wang, Y Sempowski, G Saunders, KO Borrow, P Haynes, BF |
| author_facet | Li, D Bradley, T Cain, DW Pedroza-Pacheco, I Aggelakopoulou, M Parks, R Barr, M Xia, S-M Scearce, R Bowman, C Stevens, G Newman, A Hora, B Chen, Y Riebe, K Wang, Y Sempowski, G Saunders, KO Borrow, P Haynes, BF |
| author_sort | Li, D |
| collection | OXFORD |
| description | Rab11 recycling endosomes are involved in immunological synaptic functions, but the roles of Rab11 family-interacting protein 5 (Rab11Fip5), one of the Rab11 effectors, in the immune system remain obscure. Our previous study demonstrated that RAB11FIP5 transcripts are significantly elevated in PBMCs from HIV-1-infected individuals, making broadly HIV-1-neutralizing Abs compared with those without broadly neutralizing Abs; however, the role of Rab11FiP5 in immune functions remains unclear. In this study, a RAB11FIP5 gene knockout (RAB11FIP5 -/-) mouse model was employed to study the role of Rab11Fip5 in immune responses. RAB11FIP5 -/- mice exhibited no perturbation in lymphoid tissue cell subsets, and Rab11Fip5 was not required for serum Ab induction following HIV-1 envelope immunization, Ab transcytosis to mucosal sites, or survival after influenza challenge. However, differences were observed in multiple transcripts, including cytokine genes, in lymphocyte subsets from envelope-immunized RAB11FIP5 -/- versus control mice. These included alterations in several genes in NK cells that mirrored observations in NKs from HIV-infected humans expressing less RAB11FIP5, although Rab11Fip5 was dispensable for NK cell cytolytic activity. Notably, immunized RAB11FIP5 -/- mice had lower IL4 expression in CD4+ T follicular helper cells and showed lower TNF expression in CD8+ T cells. Likewise, TNF-α production by human CD8+ T cells correlated with PBMC RAB11FIP5 expression. These observations in RAB11FIP5 -/- mice suggest a role for Rab11Fip5 in regulating cytokine responses. |
| first_indexed | 2024-03-07T06:32:31Z |
| format | Journal article |
| id | oxford-uuid:f67f6dd5-d5b9-481c-b3fa-a96afad4e542 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:32:31Z |
| publishDate | 2020 |
| publisher | American Association of Immunologists |
| record_format | dspace |
| spelling | oxford-uuid:f67f6dd5-d5b9-481c-b3fa-a96afad4e5422022-03-27T12:35:33ZRAB11FIP5-deficient mice exhibit cytokine-related transcriptomic signaturesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f67f6dd5-d5b9-481c-b3fa-a96afad4e542EnglishSymplectic ElementsAmerican Association of Immunologists2020Li, DBradley, TCain, DWPedroza-Pacheco, IAggelakopoulou, MParks, RBarr, MXia, S-MScearce, RBowman, CStevens, GNewman, AHora, BChen, YRiebe, KWang, YSempowski, GSaunders, KOBorrow, PHaynes, BFRab11 recycling endosomes are involved in immunological synaptic functions, but the roles of Rab11 family-interacting protein 5 (Rab11Fip5), one of the Rab11 effectors, in the immune system remain obscure. Our previous study demonstrated that RAB11FIP5 transcripts are significantly elevated in PBMCs from HIV-1-infected individuals, making broadly HIV-1-neutralizing Abs compared with those without broadly neutralizing Abs; however, the role of Rab11FiP5 in immune functions remains unclear. In this study, a RAB11FIP5 gene knockout (RAB11FIP5 -/-) mouse model was employed to study the role of Rab11Fip5 in immune responses. RAB11FIP5 -/- mice exhibited no perturbation in lymphoid tissue cell subsets, and Rab11Fip5 was not required for serum Ab induction following HIV-1 envelope immunization, Ab transcytosis to mucosal sites, or survival after influenza challenge. However, differences were observed in multiple transcripts, including cytokine genes, in lymphocyte subsets from envelope-immunized RAB11FIP5 -/- versus control mice. These included alterations in several genes in NK cells that mirrored observations in NKs from HIV-infected humans expressing less RAB11FIP5, although Rab11Fip5 was dispensable for NK cell cytolytic activity. Notably, immunized RAB11FIP5 -/- mice had lower IL4 expression in CD4+ T follicular helper cells and showed lower TNF expression in CD8+ T cells. Likewise, TNF-α production by human CD8+ T cells correlated with PBMC RAB11FIP5 expression. These observations in RAB11FIP5 -/- mice suggest a role for Rab11Fip5 in regulating cytokine responses. |
| spellingShingle | Li, D Bradley, T Cain, DW Pedroza-Pacheco, I Aggelakopoulou, M Parks, R Barr, M Xia, S-M Scearce, R Bowman, C Stevens, G Newman, A Hora, B Chen, Y Riebe, K Wang, Y Sempowski, G Saunders, KO Borrow, P Haynes, BF RAB11FIP5-deficient mice exhibit cytokine-related transcriptomic signatures |
| title | RAB11FIP5-deficient mice exhibit cytokine-related transcriptomic signatures |
| title_full | RAB11FIP5-deficient mice exhibit cytokine-related transcriptomic signatures |
| title_fullStr | RAB11FIP5-deficient mice exhibit cytokine-related transcriptomic signatures |
| title_full_unstemmed | RAB11FIP5-deficient mice exhibit cytokine-related transcriptomic signatures |
| title_short | RAB11FIP5-deficient mice exhibit cytokine-related transcriptomic signatures |
| title_sort | rab11fip5 deficient mice exhibit cytokine related transcriptomic signatures |
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