| First Author | Ma C | Year | 2022 |
| Journal | J Leukoc Biol | Volume | 112 |
| Issue | 6 | Pages | 1387-1397 |
| PubMed ID | 35916034 | Mgi Jnum | J:332185 |
| Mgi Id | MGI:7411349 | Doi | 10.1002/JLB.1A0122-080R |
| Citation | Ma C, et al. (2022) Selenoprotein I deficiency in T cells promotes differentiation into tolerant phenotypes while decreasing Th17 pathology. J Leukoc Biol 112(6):1387-1397 |
| abstractText | Selenoprotein I (SELENOI) is an ethanolamine phospholipid transferase contributing to cellular metabolism and the synthesis of glycosylphosphatidylinositol (GPI) anchors. SELENOI knockout (KO) in T cells has been shown to impair metabolic reprogramming during T cell activation and reduce GPI-anchored Thy-1 levels, which are both crucial for Th17 differentiation. This suggests SELENOI may be important for Th17 differentiation, and we found that SELENOI was indeed up-regulated early during the activation of naive CD4(+) T cells in Th17 conditions. SELENOI KO reduced RORgammat mRNA levels by decreasing SOX5 and STAT3 binding to promoter and enhancer regions in the RORC gene encoding this master regulator of Th17 cell differentiation. Differentiation of naive CD4(+) T cells into inflammatory versus tolerogenic Th cell subsets was analyzed and results showed that SELENOI deficiency skewed differentiation away from pathogenic Th17 cells (RORgammat(+) and IL-17A(+) ) while promoting tolerogenic phenotypes (Foxp3(+) and IL-10(+) ). Wild-type and T cell-specific SELENOI KO mice were subjected to experimental autoimmune encephalitis (EAE), with KO mice exhibiting diminished clinical symptoms, reduced CNS pathology and decreased T cell infiltration. Flow cytometry showed that SELENOI T cell KO mice exhibited lower CD4(+) RORgammat(+) and CD4(+) IL-17A(+) T cells and higher CD4(+) CD25(+) FoxP3(+) T cells in CNS tissues of mice subjected to EAE. Thus, the metabolic enzyme SELENOI is up-regulated to promote RORgammat transcription that drives Th17 differentiation, and SELENOI deficiency shifts differentiation toward tolerogenic phenotypes while protecting against pathogenic Th17 responses. |
