MicroRNA-181a/b-1 Is Not Required for Innate γδ NKT Effector Cell Development
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MicroRNA-181a/b-1 Is Not Required for Innate γδ NKT Effector Cell Development. / Sandrock, Inga; Ziętara, Natalia; Łyszkiewicz, Marcin; Oberdörfer, Linda; Witzlau, Katrin; Krueger, Andreas; Prinz, Immo.
In: PLOS ONE, Vol. 10, No. 12, 16.12.2015, p. e0145010.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - MicroRNA-181a/b-1 Is Not Required for Innate γδ NKT Effector Cell Development
AU - Sandrock, Inga
AU - Ziętara, Natalia
AU - Łyszkiewicz, Marcin
AU - Oberdörfer, Linda
AU - Witzlau, Katrin
AU - Krueger, Andreas
AU - Prinz, Immo
PY - 2015/12/16
Y1 - 2015/12/16
N2 - Thymic development of αβ T lymphocytes into invariant natural killer (NK) T cells depends on their selection via agonistic lipid antigen presented by CD1d. If successful, newly selected NKT cells gain effector functions already in the thymus. Some γδ T cell subsets also acquire effector functions in the thymus. However, it is not clear whether agonistic TCR stimulation is involved in thymic γδ T cell selection and development. Here we combine two genetic models to address this question. MiR-181a/b-1-/-mice, which show impaired agonistic T cell selection of invariant αβ NKT cells, were crossed to Tcrd-H2BeGFP reporter mice to monitor selection, intra-thymic expansion and differentiation of γδ T cells. We found that miR-181a/b-1-deficiency had no effect on numbers of thymic γδ T cell or on their differentiation towards an IL-17- or IFN-γ-producing effector phenotype. Also, the composition of peripheral lymph node γδ T cells was not affected by miR-181a/b-1-deficiency. Dendritic epidermal γδ T cells were normally present in knock-out animals. However, we observed elevated frequencies and numbers of γδ NKT cells in the liver, possibly because γδ NKT cells can expand and replace missing αβ NKT cells in peripheral niches. In summary, we investigated the role of miR-181a/b-1 for selection, intrathymic development and homeostasis of γδ T cells. We conclude that miR-181a/b-1-dependent modulation of T cell selection is not critically required for innate development of γδ NKT cells or of any other γδ T cell subtypes.
AB - Thymic development of αβ T lymphocytes into invariant natural killer (NK) T cells depends on their selection via agonistic lipid antigen presented by CD1d. If successful, newly selected NKT cells gain effector functions already in the thymus. Some γδ T cell subsets also acquire effector functions in the thymus. However, it is not clear whether agonistic TCR stimulation is involved in thymic γδ T cell selection and development. Here we combine two genetic models to address this question. MiR-181a/b-1-/-mice, which show impaired agonistic T cell selection of invariant αβ NKT cells, were crossed to Tcrd-H2BeGFP reporter mice to monitor selection, intra-thymic expansion and differentiation of γδ T cells. We found that miR-181a/b-1-deficiency had no effect on numbers of thymic γδ T cell or on their differentiation towards an IL-17- or IFN-γ-producing effector phenotype. Also, the composition of peripheral lymph node γδ T cells was not affected by miR-181a/b-1-deficiency. Dendritic epidermal γδ T cells were normally present in knock-out animals. However, we observed elevated frequencies and numbers of γδ NKT cells in the liver, possibly because γδ NKT cells can expand and replace missing αβ NKT cells in peripheral niches. In summary, we investigated the role of miR-181a/b-1 for selection, intrathymic development and homeostasis of γδ T cells. We conclude that miR-181a/b-1-dependent modulation of T cell selection is not critically required for innate development of γδ NKT cells or of any other γδ T cell subtypes.
KW - Animals
KW - Antigens, CD1d/metabolism
KW - Cell Differentiation/genetics
KW - Clonal Selection, Antigen-Mediated/genetics
KW - Immunity, Innate
KW - Immunophenotyping
KW - Liver/cytology
KW - Lymph Nodes/cytology
KW - Mice
KW - Mice, Knockout
KW - Mice, Transgenic
KW - MicroRNAs/genetics
KW - Natural Killer T-Cells/cytology
KW - Phenotype
KW - Receptors, Antigen, T-Cell, gamma-delta/metabolism
KW - T-Cell Antigen Receptor Specificity/immunology
KW - T-Lymphocyte Subsets/cytology
KW - Thymus Gland/cytology
U2 - 10.1371/journal.pone.0145010
DO - 10.1371/journal.pone.0145010
M3 - SCORING: Journal article
C2 - 26673421
VL - 10
SP - e0145010
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 12
ER -