T cell-expressed Ift88 is required for proper thymocyte differentiation in mice

Physiol Rep. 2024 Nov;12(22):e70120. doi: 10.14814/phy2.70120.

Abstract

Intraflagellar transport protein 88 (Ift88) is required for the formation of cilia in the thymus and non-ciliary dependent functions including T cell immune synapse formation. To test the role of Ift88 in T cell development, we performed flow cytometry analysis on thymus and spleen tissue isolated from mice lacking Ift88 in thymic epithelial cells (TECs) or T cells. Analyses indicated that TEC Ift88 deletion had no impact on thymic T cell development and minimal impact on splenic T cells. Analysis of T cells in CaggCreERT2+Ift88 tm1BkymTmG mice indicate that approximately half of DN1 thymocytes are Ift88 deficient 3 weeks post-tamoxifen induction; Ift88 loss did not impact T cell development at the DN2-DN4 stage or the CD4+/CD8+ double-positive (DP) thymocyte stage. However, survival of Ift88 deficient T cells was significantly reduced at the single-positive (SP) thymocyte stage, as was the number of CD4+ and CD8+ T cells in spleen and kidney. Despite preferential survival of Ift88-proficient cells, the total number of T cells the in spleen and kidney was minimally impacted by Ift88 loss. These data suggest Ift88 is required for differentiation of DP thymocytes into SP thymocytes and that Ift88 proficient T cells can compensate for deficient cells to fill the open niche.

Keywords: thymocyte development; thymus.

MeSH terms

  • Animals
  • Cell Differentiation*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • T-Lymphocytes / cytology
  • T-Lymphocytes / metabolism
  • Thymocytes* / cytology
  • Thymocytes* / metabolism
  • Thymus Gland / cytology
  • Thymus Gland / metabolism
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism

Substances

  • Tg737Rpw protein, mouse
  • Tumor Suppressor Proteins