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 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.