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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 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.


Li, Dapeng, Todd Bradley, Derek W. Cain, Isabela Pedroza-Pacheco, Maria Aggelakopoulou, Robert Parks, Maggie Barr, et al. “RAB11FIP5-Deficient Mice Exhibit Cytokine-Related Transcriptomic Signatures.” Immunohorizons 4, no. 11 (November 10, 2020): 713–28.

Published Date: 
Tuesday, November 10, 2020
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