RAB11FIP5-Deficient Mice Exhibit Cytokine-Related Transcriptomic Signatures

Immunohorizons. 2020 Nov 10;4(11):713-728. 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 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / deficiency
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / immunology*
  • Animals
  • Antibodies, Neutralizing / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • Cytokines / metabolism
  • Female
  • HIV Infections / immunology*
  • HIV Infections / physiopathology
  • HIV-1 / pathogenicity
  • Humans
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Transcriptome*

Substances

  • Adaptor Proteins, Signal Transducing
  • Antibodies, Neutralizing
  • Cytokines
  • RAB11FIP5 protein, human