Loss of Canonical Notch Signaling Affects Multiple Steps in NK Cell Development in Mice

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Loss of Canonical Notch Signaling Affects Multiple Steps in NK Cell Development in Mice. / Chaves, Patricia; Zriwil, Alya; Wittmann, Lilian; Boukarabila, Hanane; Peitzsch, Claudia; Jacobsen, Sten Eirik W.; Sitnicka, Ewa.

In: Journal of immunology (Baltimore, Md. : 1950), Vol. 201, No. 11, 2018, p. 3307-3319.

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Chaves, Patricia ; Zriwil, Alya ; Wittmann, Lilian ; Boukarabila, Hanane ; Peitzsch, Claudia ; Jacobsen, Sten Eirik W. ; Sitnicka, Ewa. / Loss of Canonical Notch Signaling Affects Multiple Steps in NK Cell Development in Mice. In: Journal of immunology (Baltimore, Md. : 1950). 2018 ; Vol. 201, No. 11. pp. 3307-3319.

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TY - JOUR

T1 - Loss of Canonical Notch Signaling Affects Multiple Steps in NK Cell Development in Mice

AU - Chaves, Patricia

AU - Zriwil, Alya

AU - Wittmann, Lilian

AU - Boukarabila, Hanane

AU - Peitzsch, Claudia

AU - Jacobsen, Sten Eirik W.

AU - Sitnicka, Ewa

PY - 2018

Y1 - 2018

N2 - Within the hematopoietic system, the Notch pathway is critical for promoting thymic T cell development and suppressing the B and myeloid lineage fates; however, its impact on NK lymphopoiesis is less understood. To study the role of Notch during NK cell development in vivo, we investigated different NK cell compartments and function in Rbp-Jkfl/flVav-Cretg/+ mice, in which Rbp-Jk, the major transcriptional effector of canonical Notch signaling, was specifically deleted in all hematopoietic cells. Peripheral conventional cytotoxic NK cells in Rbp-Jk-deleted mice were significantly reduced and had an activated phenotype. Furthermore, the pool of early NK cell progenitors in the bone marrow was decreased, whereas immature NK cells were increased, leading to a block in NK cell maturation. These changes were cell intrinsic as the hematopoietic chimeras generated after transplantation of Rbp-Jk-deficient bone marrow cells had the same NK cell phenotype as the Rbp-Jk-deleted donor mice, whereas the wild-type competitors did not. The expression of several crucial NK cell regulatory pathways was significantly altered after Rbp-Jk deletion. Together, these results demonstrate the involvement of canonical Notch signaling in regulation of multiple stages of NK cell development.

AB - Within the hematopoietic system, the Notch pathway is critical for promoting thymic T cell development and suppressing the B and myeloid lineage fates; however, its impact on NK lymphopoiesis is less understood. To study the role of Notch during NK cell development in vivo, we investigated different NK cell compartments and function in Rbp-Jkfl/flVav-Cretg/+ mice, in which Rbp-Jk, the major transcriptional effector of canonical Notch signaling, was specifically deleted in all hematopoietic cells. Peripheral conventional cytotoxic NK cells in Rbp-Jk-deleted mice were significantly reduced and had an activated phenotype. Furthermore, the pool of early NK cell progenitors in the bone marrow was decreased, whereas immature NK cells were increased, leading to a block in NK cell maturation. These changes were cell intrinsic as the hematopoietic chimeras generated after transplantation of Rbp-Jk-deficient bone marrow cells had the same NK cell phenotype as the Rbp-Jk-deleted donor mice, whereas the wild-type competitors did not. The expression of several crucial NK cell regulatory pathways was significantly altered after Rbp-Jk deletion. Together, these results demonstrate the involvement of canonical Notch signaling in regulation of multiple stages of NK cell development.

U2 - 10.4049/jimmunol.1701675

DO - 10.4049/jimmunol.1701675

M3 - Article

VL - 201

SP - 3307

EP - 3319

JO - Journal of immunology (Baltimore, Md. : 1950)

T2 - Journal of immunology (Baltimore, Md. : 1950)

JF - Journal of immunology (Baltimore, Md. : 1950)

SN - 1550-6606

IS - 11

ER -