TGF-β is responsible for NK cell immaturity during ontogeny and increased susceptibility to infection during mouse infancy

Marcoe, Jeffrey P; Lim, James Ray; Schaubert, Keri L.; Fodil-Cornu, Nassima; Matka, Marsel; McCubbrey, Alexandra L.; Farr, Alexander R.; Vidal, Silvia M.; Laouar, Yasmina

doi:10.1038/ni.2388

Cited by 119 publications

(130 citation statements)

References 46 publications

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“…In neonates, blocking TGF-b signaling on NK cells promotes faster NK maturation and reduces susceptibility of neonates to viral infection (Marcoe et al 2012). In adults, TGF-b inhibits IFN-g and T-bet expression in NK cells, thus inhibiting type 1 immunity (Laouar et al 2005;Yu et al 2006).…”

Section: Nk Cellsmentioning

confidence: 99%

Regulation of the Immune Response by TGF-β: From Conception to Autoimmunity and Infection

Sanjabi

2017

Cold Spring Harb Perspect Biol

452

306

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Transforming growth factor b (TGF-b) is a pleiotropic cytokine involved in both suppressive and inflammatory immune responses. After 30 years of intense study, we have only begun to elucidate how TGF-b alters immunity under various conditions. Under steady-state conditions, TGF-b regulates thymic T-cell selection and maintains homeostasis of the naïve T-cell pool. TGF-b inhibits cytotoxic T lymphocyte (CTL), Th1-, and Th2-cell differentiation while promoting peripheral ( p)Treg-, Th17-, Th9-, and Tfh-cell generation, and T-cell tissue residence in response to immune challenges. Similarly, TGF-b controls the proliferation, survival, activation, and differentiation of B cells, as well as the development and functions of innate cells, including natural killer (NK) cells, macrophages, dendritic cells, and granulocytes. Collectively, TGF-b plays a pivotal role in maintaining peripheral tolerance against self-and innocuous antigens, such as food, commensal bacteria, and fetal alloantigens, and in controlling immune responses to pathogens.

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Section: Nk Cellsmentioning

confidence: 99%

Regulation of the Immune Response by TGF-β: From Conception to Autoimmunity and Infection

Sanjabi

2017

Cold Spring Harb Perspect Biol

452

306

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“…Moreover, TGF-b is constitutively present in the CSF and was found to modulate macrophages (82). Because TGF-b was recently shown to negatively regulate maturation of NK cells, it might be relevant to investigate ex vivo whether particular CSF constituents might modify NK cell phenotypes (83). The reason for the presence of immature NK cells in the healthy CNS needs further experiments to delineate whether the brain influx of NK cells is dependent on their phenotype or whether it is the CNS milieu that further influences such influx.…”

Section: Nk Cell Modifications Associated With Cns Disordersmentioning

confidence: 99%

NK Cells in Central Nervous System Disorders

Poli

Kmiecik

Domingues

et al. 2013

The Journal of Immunology

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NK cells are important players in immunity against pathogens and neoplasms. As a component of the innate immune system, they are one of the first effectors on sites of inflammation. Through their cytokine production capacities, NK cells participate in the development of a potent adaptive immune response. Furthermore, NK cells were found to have regulatory functions to limit and prevent autoimmunity via killing of autologous immune cells. These paradoxical functions of NK cells are reflected in CNS disorders. In this review, we discuss the phenotypes and functional features of peripheral and brain NK cells in brain tumors and infections, neurodegenerative diseases, acute vascular and traumatic damage, as well as mental disorders. We also discuss the implication of NK cells in neurotoxicity and neuroprotection following CNS pathology, as well as the crosstalk between NK cells and brain-resident immune cells.

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“…What about NK cell differentiation? A recent article from Marcoe et al 66 demonstrated that TGF-b limits NK cell numbers in mice by controlling NK cell maturation. In fact, in the absence of TGF-b, ontogenic maturation from HSC to NK cells was faster.…”

Section: Interaction Between Nk Cells and Treg Cells In Hematopoieticmentioning

confidence: 99%

Interaction between natural killer cells and regulatory T cells: perspectives for immunotherapy

2013

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Regulatory T (Treg) cells and natural killer (NK) cells are key players in the immune system. The interaction between these two cell types has been reported to be beneficial in healthy conditions such as pregnancy. However, in the case of certain pathologies such as autoimmune diseases and cancer this interaction can become detrimental, as Treg cells have been described to suppress NK cells and in particular to impair NK cell effector functions. This review aims to discuss the recent information on the interaction between Treg cells and NK cells under healthy and pathologic conditions, to describe the specific conditions in which this interaction takes place, the effect of Treg cells on hematopoietic stem cell differentiation and the consequences of this interaction on the optimization of immunotherapeutic protocols.

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TGF-β is responsible for NK cell immaturity during ontogeny and increased susceptibility to infection during mouse infancy

Cited by 119 publications

References 46 publications

Regulation of the Immune Response by TGF-β: From Conception to Autoimmunity and Infection

Regulation of the Immune Response by TGF-β: From Conception to Autoimmunity and Infection

NK Cells in Central Nervous System Disorders

Interaction between natural killer cells and regulatory T cells: perspectives for immunotherapy

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