Carcinoembryonic Antigen-Related Cell Adhesion Molecule-1 Regulates Granulopoiesis by Inhibition of Granulocyte Colony-Stimulating Factor Receptor

Pan, Hao; Shively, John E.

doi:10.1016/j.immuni.2010.10.009

Cited by 54 publications

(79 citation statements)

References 32 publications

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“…1). As previously reported [34][35][36] , high levels of CEACAM1 expression were detected on blood granulocytes (Ly6G þ ) and monocytes (CD115 þ ) with the anti-CEACAM1-specific monoclonal antibody (clone CC1, Fig. 1a).…”

Section: Ceacam1 Is Expressed On B-cell Subsetssupporting

confidence: 84%

CEACAM1 induces B-cell survival and is essential for protective antiviral antibody production

et al. 2016

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B cells are essential for antiviral immune defence because they produce neutralizing antibodies, present antigen and maintain the lymphoid architecture. Here we show that intrinsic signalling of CEACAM1 is essential for generating efficient B-cell responses. Although CEACAM1 exerts limited influence on the proliferation of B cells, expression of CEACAM1 induces survival of proliferating B cells via the BTK/Syk/NF-kB-axis. The absence of this signalling cascade in naive Ceacam1 À / À mice limits the survival of B cells. During systemic infection with cytopathic vesicular stomatitis virus, Ceacam1 À / À mice can barely induce neutralizing antibody responses and die early after infection. We find, therefore, that CEACAM1 is a crucial regulator of B-cell survival, influencing B-cell numbers and protective antiviral antibody responses.

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Section: Ceacam1 Is Expressed On B-cell Subsetssupporting

confidence: 84%

CEACAM1 induces B-cell survival and is essential for protective antiviral antibody production

et al. 2016

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“…9 In comparison, CEACAM1 plays a key role in SHP-1-dependent expansion of bone marrow neutrophils via blocking granulocyte macrophage-CSF-signal transducer and activator of transcription 3 signaling. 42 A recent study has shown that CEACAM1 can also regulate TLR-4-triggered inflammasome activation via SHP-1-dependent negative regulation of Syk activation. 43 The Figure 7.…”

Section: Discussionmentioning

confidence: 99%

Siglec-E is a negative regulator of acute pulmonary neutrophil inflammation and suppresses CD11b β2-integrin–dependent signaling

McMillan

Sharma

McKenzie

et al. 2013

Blood

105

138

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“…26,41 However, Wip1 may mainly regulate the relatively late stage of neutrophil development from its progenitor cells. It is somewhat consistent with the observation that Wip1 expression increases during the differentiation of GMPs into mature neutrophils, whereas HSCs express low levels of Wip1.…”

Section: Discussionmentioning

confidence: 99%

Phosphatase Wip1 negatively regulates neutrophil development through p38 MAPK-STAT1

Liu

Sun

et al. 2013

Blood

104

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IntroductionPolymorphonuclear neutrophil granulocytes (PMNs or neutrophils) develop in the bone marrow (BM). They are fully equipped with a variety of granules, which contain proteases that enable the neutrophils to deliver lethal hits against invading microorganisms. 1,2 Although neutrophils are essential to host defense against intruding microorganisms and play a critical role in initiating inflammation and innate immunity, they also contribute to the pathology of various acute and chronic inflammatory conditions. 3,4 In this manner, means to properly control the development, homeostasis, and functional activities of neutrophils is of central importance to mounting robust host defense responses and simultaneously avoiding tissue damage. 5,6 However, the molecular mechanisms that accomplish this balanced effect remain poorly understood.Wild-type (WT) p53-induced phosphatase 1 (Wip1, also called PP2C␦), which is encoded by protein phophatase magnesiumdependent 1delta (PPm1D), is a serine/threonine protein phosphatase belonging to the type 2C␦ protein phosphatases. 7 It is activated by various stresses and involved in various cellular processes, such as tumorigenesis and aging. 8,9 Wip1, overexpressed in many cancers, is recognized as a novel oncogene inhibiting several p53-dependent tumor suppressor pathways, such as ATM-CHK2-p53 and p38 MAPK-p53 pathways as well as the NF-B pathway. [10][11][12][13] Currently, Wip1 is thought to be a promising drug target for cancer therapy. In the present study, after observing that Wip1 is specifically expressed in resting neutrophils among all immune cells and is up-regulated gradually during neutrophil maturation, we used Wip1-deficient mice to investigate the role of Wip1 in neutrophil development and homeostasis. Notably, Wip1-deficient mice displayed neutrophilia with significantly expanded granulocytic differentiation and hypermaturation phenotype in a cell-intrinsic and specific manner. Thus, phosphatase Wip1, as a key feedback regulator, negatively controls granulocytopoiesis and peripheral neutrophil homeostasis. Methods MiceC57BL/6 and CD45.1 ϩ mice were purchased from Beijing University Experimental Animal Center (Beijing, China). Wip1 Ϫ/Ϫ , p53 ϩ/Ϫ , and p38 ϩ/Ϫ mice were kindly provided by the Key Laboratory of Human Diseases Comparative Medicine, the Ministry of Public Health (Beijing, China). Wip1 Ϫ/Ϫ mice have been described 10,14 and backcrossed to the C57BL/6 background in our laboratory. Wip1 Ϫ/Ϫ and p53 ϩ/Ϫ mice were mated to obtain Wip1 Ϫ/Ϫ p53 Ϫ/Ϫ double-knockout mice. All mice were bred and maintained in specific pathogen-free conditions. Sex-matched littermate mice 6-12 weeks of age were mainly used for experiments unless otherwise noted. Complete or mixed chimeras were generated by transferring 1 to 2 ϫ 10 7 BM cells (BMCs) from either WT and/or Wip1KO mice into lethally irradiated mice. 15,16 Animal protocols were approved by the Animal Ethics Committee of the Institute of Zoology, Beijing, China. *G.L., X.H., and B.S. contributed equally to this st...

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Carcinoembryonic Antigen-Related Cell Adhesion Molecule-1 Regulates Granulopoiesis by Inhibition of Granulocyte Colony-Stimulating Factor Receptor

Cited by 54 publications

References 32 publications

CEACAM1 induces B-cell survival and is essential for protective antiviral antibody production

CEACAM1 induces B-cell survival and is essential for protective antiviral antibody production

Siglec-E is a negative regulator of acute pulmonary neutrophil inflammation and suppresses CD11b β2-integrin–dependent signaling

Phosphatase Wip1 negatively regulates neutrophil development through p38 MAPK-STAT1

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