RAB11FIP5-Deficient Mice Exhibit Cytokine-Related Transcriptomic Signatures.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • November 10, 2020

Published In

Volume / Issue

  • 4 / 11

Start / End Page

  • 713 - 728

PubMed ID

  • 33172842

Pubmed Central ID

  • PMC8050958

Electronic International Standard Serial Number (EISSN)

  • 2573-7732

Digital Object Identifier (DOI)

  • 10.4049/immunohorizons.2000088

Language

  • eng

Conference Location

  • United States