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ImmunoHorizons
11 10, 2020;4 (11): 713-728.

-Deficient Mice Exhibit Cytokine-Related Transcriptomic Signatures.

Dapeng Li, Todd Bradley, Derek W Cain, Isabela Pedroza-Pacheco, Maria Aggelakopoulou, Robert Parks, Maggie Barr, Shi-Mao Xia, Richard Scearce, Cindy Bowman, Grace Stevens, Amanda Newman, Bhavna Hora, Yue Chen, Kristina Riebe, Yunfei Wang, Gregory Sempowski, Kevin O Saunders, Persephone Borrow, Barton F Haynes
Author Information
  1. Dapeng Li: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710; dapeng.li@duke.edu barton.haynes@duke.edu.
  2. Todd Bradley: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710.
  3. Derek W Cain: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710.
  4. Isabela Pedroza-Pacheco: Nuffield Department of Clinical Medicine, University of Oxford, OX3 7FZ Oxford, United Kingdom.
  5. Maria Aggelakopoulou: Nuffield Department of Clinical Medicine, University of Oxford, OX3 7FZ Oxford, United Kingdom.
  6. Robert Parks: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710.
  7. Maggie Barr: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710.
  8. Shi-Mao Xia: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710.
  9. Richard Scearce: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710.
  10. Cindy Bowman: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710. ORCID
  11. Grace Stevens: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710. ORCID
  12. Amanda Newman: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710.
  13. Bhavna Hora: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710.
  14. Yue Chen: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710.
  15. Kristina Riebe: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710. ORCID
  16. Yunfei Wang: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710.
  17. Gregory Sempowski: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710.
  18. Kevin O Saunders: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710. ORCID
  19. Persephone Borrow: Nuffield Department of Clinical Medicine, University of Oxford, OX3 7FZ Oxford, United Kingdom. ORCID
  20. Barton F Haynes: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710; dapeng.li@duke.edu barton.haynes@duke.edu.
PMID: 33172842 DOI: 10.4049/immunohorizons.2000088

Abstract

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 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 gene knockout ( ) mouse model was employed to study the role of Rab11Fip5 in immune responses. 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 versus control mice. These included alterations in several genes in NK cells that mirrored observations in NKs from HIV-infected humans expressing less , although Rab11Fip5 was dispensable for NK cell cytolytic activity. Notably, immunized mice had lower expression in CD4 T follicular helper cells and showed lower expression in CD8 T cells. Likewise, TNF-α production by human CD8 T cells correlated with PBMC expression. These observations in mice suggest a role for Rab11Fip5 in regulating cytokine responses.

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Grants

  1. UM1 AI100645/NIAID NIH HHS
  2. MR/K012037/1/Medical Research Council
  3. UC6 AI058607/NIAID NIH HHS
  4. R01 AI147778/NIAID NIH HHS
  5. UM1 AI144371/NIAID NIH HHS

MeSH Term

Adaptor Proteins, Signal Transducing
Animals
Antibodies, Neutralizing
CD8-Positive T-Lymphocytes
Cytokines
Female
HIV Infections
HIV-1
Humans
Killer Cells, Natural
Male
Mice
Mice, Inbred C57BL
Transcriptome

Chemicals

Adaptor Proteins, Signal Transducing
Antibodies, Neutralizing
Cytokines
RAB11FIP5 protein, human
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't
Article has an altmetric score of 4

Word Cloud

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