title: Differential requirement for the CD45 splicing regulator hnRNPLL for accumulation of NKT and conventional T cells.
abstract: Natural killer T (NKT) cells represent an important regulatory T cell subset that develops in the thymus and contains immature (NK1.1(lo)) and mature (NK1.1(hi)) cell subsets. Here we show in mice that an inherited mutation in heterogeneous ribonucleoprotein L-like protein (hnRNPLL(thunder)), that shortens the survival of conventional T cells, has no discernible effect on NKT cell development, homeostasis or effector function. Thus, Hnrpll deficiency effectively increases the NKT∶T cell ratio in the periphery. However, Hnrpll mutation disrupts CD45RA, RB and RC exon silencing of the Ptprc mRNA in both NKT and conventional T cells, and leads to a comparably dramatic shift to high molecular weight CD45 isoforms. In addition, Hnrpll mutation has a cell intrinsic effect on the expression of the developmentally regulated cell surface marker NK1.1 on NKT cells in the thymus and periphery but does not affect cell numbers. Therefore our results highlight both overlapping and divergent roles for hnRNPLL between conventional T cells and NKT cells. In both cell subsets it is required as a trans-acting factor to regulate alternative splicing of the Ptprc mRNA, but it is only required for survival of conventional T cells.
authors.affiliation: Department of Immunology, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Yabas
authors.forename: Dale I
authors.initials: DI
authors.lastname: Godfrey
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Goodnow
authors.forename: Gerard F
authors.initials: GF
authors.lastname: Hoyne
mesh_terms: D000818:Animals; D005091:Exons; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000502:physiology*; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D034441:Heterogeneous-Nuclear Ribonucleoproteins; C534662:hnRNPLL protein, mouse; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse
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