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Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets
Published on: April 16, 2015
Cutting Edge: Eomesodermin Is Sufficient To Direct Type 1 Innate Lymphocyte Development into the Conventional NK
Olga Pikovskaya1, Julie Chaix1, Nyanza J Rothman1
1Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032; Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032;
Type 1 innate lymphocytes, including helper ILC1s and NK cells, require both T-bet and Eomes for development. Ectopic Eomes expression can redirect helper ILC1s towards a natural killer cell fate, revealing developmental plasticity.
Area of Science:
- Immunology
- Cell Biology
- Developmental Biology
Background:
- Type 1 innate lymphocytes (ILCs) encompass type 1 helper ILCs (hILC1s) and conventional NK cells (cNKs).
- Both lineages express T-bet, but cNKs uniquely express Eomesodermin (Eomes).
- The distinct roles of T-bet and Eomes in type 1 ILC development are not fully elucidated.
Purpose of the Study:
- To investigate the necessity of Eomes for conventional NK cell development.
- To determine if Eomes is sufficient to confer conventional NK cell characteristics onto type 1 helper ILCs.
- To explore the developmental plasticity of type 1 innate lymphoid cells.
Main Methods:
- Utilized NKp46-Cre mice to delete Eomes alleles during type 1 ILC maturation.
- Generated transgenic mice expressing Eomes under the control of the Tbx21 locus.
- Analyzed the lymphoid and nonlymphoid type 1 ILC compartments in genetically modified mice.
Main Results:
- Deletion of Eomes significantly blocked conventional NK cell development.
- The formation of the type 1 ILC compartment depends on the semiredundant functions of T-bet and Eomes.
- Ectopic Eomes expression induced conventional NK cell-like properties in both lymphoid and nonlymphoid type 1 ILCs.
Conclusions:
- Eomes is crucial for conventional NK cell lineage commitment.
- T-bet and Eomes act semiredundantly in the development of all type 1 ILCs.
- Type 1 innate lymphoid cells exhibit significant developmental plasticity post-lineage specification.
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