The Role of Cytokine-Inducible SH2 Domain-Containing Protein (CISH) in the Regulation of Basal and Cytokine-Mediated Myelopoiesis

Cytokine-inducible SH2 domain-containing protein (CISH) is a member of the suppressor of cytokine signaling (SOCS) family of negative feedback regulators shown to play crucial roles in lymphoid cell development and function as well as appetite regulation. It has also been implicated in the control o...

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Main Authors: Wasan Naser, Saeed Maymand, Daniel Dlugolenski, Faiza Basheer, Alister C. Ward
Format: Article
Language:English
Published: MDPI AG 2023-08-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/16/12757
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author Wasan Naser
Saeed Maymand
Daniel Dlugolenski
Faiza Basheer
Alister C. Ward
author_facet Wasan Naser
Saeed Maymand
Daniel Dlugolenski
Faiza Basheer
Alister C. Ward
author_sort Wasan Naser
collection DOAJ
description Cytokine-inducible SH2 domain-containing protein (CISH) is a member of the suppressor of cytokine signaling (SOCS) family of negative feedback regulators shown to play crucial roles in lymphoid cell development and function as well as appetite regulation. It has also been implicated in the control of signaling downstream of the receptors for the cytokines granulocyte/macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) in myeloid cells. To investigate the physiological role of CISH in myelopoiesis, mice deficient in CISH were analyzed basally and in response to administration of these cytokines. CISH knockout (KO) mice possessed basally elevated neutrophils in the blood, bone marrow, and spleen compared to wild-type (WT) mice. During GM-CSF-induced myelopoiesis, the frequency of neutrophils, myeloid dendritic cells (DCs), and CFU-M in the bone marrow was higher in the KO, as were the neutrophils and CFU-G in the spleen. In contrast, no differences were observed between KO and WT mice during G-CSF-induced myelopoiesis apart from an elevated frequency of CFU-G and CFU-M in the spleen. This work has identified a role for CISH in the negative regulation of granulopoiesis, including that mediated by GM-CSF.
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spelling doaj.art-b79378e7f8fa4b22a06f92fd68c261502023-11-19T01:28:56ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124161275710.3390/ijms241612757The Role of Cytokine-Inducible SH2 Domain-Containing Protein (CISH) in the Regulation of Basal and Cytokine-Mediated MyelopoiesisWasan Naser0Saeed Maymand1Daniel Dlugolenski2Faiza Basheer3Alister C. Ward4School of Medicine, Deakin University, Geelong, VIC 3216, AustraliaSchool of Medicine, Deakin University, Geelong, VIC 3216, AustraliaSchool of Medicine, Deakin University, Geelong, VIC 3216, AustraliaSchool of Medicine, Deakin University, Geelong, VIC 3216, AustraliaSchool of Medicine, Deakin University, Geelong, VIC 3216, AustraliaCytokine-inducible SH2 domain-containing protein (CISH) is a member of the suppressor of cytokine signaling (SOCS) family of negative feedback regulators shown to play crucial roles in lymphoid cell development and function as well as appetite regulation. It has also been implicated in the control of signaling downstream of the receptors for the cytokines granulocyte/macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) in myeloid cells. To investigate the physiological role of CISH in myelopoiesis, mice deficient in CISH were analyzed basally and in response to administration of these cytokines. CISH knockout (KO) mice possessed basally elevated neutrophils in the blood, bone marrow, and spleen compared to wild-type (WT) mice. During GM-CSF-induced myelopoiesis, the frequency of neutrophils, myeloid dendritic cells (DCs), and CFU-M in the bone marrow was higher in the KO, as were the neutrophils and CFU-G in the spleen. In contrast, no differences were observed between KO and WT mice during G-CSF-induced myelopoiesis apart from an elevated frequency of CFU-G and CFU-M in the spleen. This work has identified a role for CISH in the negative regulation of granulopoiesis, including that mediated by GM-CSF.https://www.mdpi.com/1422-0067/24/16/12757CISHcytokineG-CSFGM-CSFgranulopoiesismyelopoiesis
spellingShingle Wasan Naser
Saeed Maymand
Daniel Dlugolenski
Faiza Basheer
Alister C. Ward
The Role of Cytokine-Inducible SH2 Domain-Containing Protein (CISH) in the Regulation of Basal and Cytokine-Mediated Myelopoiesis
International Journal of Molecular Sciences
CISH
cytokine
G-CSF
GM-CSF
granulopoiesis
myelopoiesis
title The Role of Cytokine-Inducible SH2 Domain-Containing Protein (CISH) in the Regulation of Basal and Cytokine-Mediated Myelopoiesis
title_full The Role of Cytokine-Inducible SH2 Domain-Containing Protein (CISH) in the Regulation of Basal and Cytokine-Mediated Myelopoiesis
title_fullStr The Role of Cytokine-Inducible SH2 Domain-Containing Protein (CISH) in the Regulation of Basal and Cytokine-Mediated Myelopoiesis
title_full_unstemmed The Role of Cytokine-Inducible SH2 Domain-Containing Protein (CISH) in the Regulation of Basal and Cytokine-Mediated Myelopoiesis
title_short The Role of Cytokine-Inducible SH2 Domain-Containing Protein (CISH) in the Regulation of Basal and Cytokine-Mediated Myelopoiesis
title_sort role of cytokine inducible sh2 domain containing protein cish in the regulation of basal and cytokine mediated myelopoiesis
topic CISH
cytokine
G-CSF
GM-CSF
granulopoiesis
myelopoiesis
url https://www.mdpi.com/1422-0067/24/16/12757
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