GSE185256
Single cell RNAseq was conducted on mice with TIPE protein knockout to identify the effect of TIPE proteins on immune response [Lung]
Mucosal surfaces are continuously exposed to, and challenged by, numerous commensal and pathogenic organisms. To guard against infections, a majority of the thymus-derived T lymphocytes are deployed at the mucosa. Although chemokines are known to be involved in the mucosal lymphocyte deployment, it is not clear whether lymphocytes enter the mucosa through directed migration or enhanced random migration.  Here we report that TIPE (tumor necrosis factor-a-induced protein 8 (TNFAIP8)-like) proteins mediate directed migration of T lymphocytes into lung, and they are crucial for mucosal immune defense against Streptococcus pneumoniae infection. Knockout of both Tnfaip8 and Tipe2, which encode polarity proteins that control the directionality of lymphocyte migration, significantly reduced the numbers of T lymphocytes in the lung of mice. Compared with wild-type mice, Tnfaip8-/- Tipe2-/- mice also developed more severe infection with more pathogens entering blood circulation upon nasal Streptococcus pneumoniae challenge. Single-cell RNA-sequencing analysis revealed that TIPE proteins selectively affected mucosal homing of a unique subpopulation of T cells, called “T cells-2”, which expresses high levels of Ccr9, Tcf7, and Rag1/2 genes. TNFAIP8 and TIPE2 appear to have overlapping functions since deficiency in both yielded the strongest phenotype. These data demonstrate that TIPE family of proteins are crucial for lung mucosal immunity. Strategies targeting TIPE proteins may help develop  mucosal vaccines or treat inflammatory diseases of the lung. Overall design: Eight to 10-week-old female naïve mice of WT, TKO, and DKO genotypes (three mice per group) were perfused with PBS, and lungs were collected. Single cell RNAseq was done using Seurat to compare immune cell differences between the 3 genotypes in lung tissues.