Common γ chain cytokines: Dissidence in the details

Alves, Nuno L.; Arosa, Fernando A.; Lier, R. A. W. Van

doi:10.1016/j.imlet.2006.11.006

Cited by 60 publications

(50 citation statements)

References 112 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…γc is an essential subunit of the receptors for the cytokines IL-2, -4, -7, -9, -15, and -21 [32] that act as critical survival and proliferation factors for lymphoid precursors and mature lymphocytes. We had previously shown that conditional ablation of Il2rg from mature NK cells resulted in the rapid disappearance of γc-deficient cells [18] underscoring the essential role for Il2rg-dependent cytokines (especially IL-15) for NK-cell homeostasis [33][34][35].…”

Section: Ablation Of Nk Cells By Generating Ncr1 Greencre Il2rg Fl/flmentioning

confidence: 99%

Conditional ablation of NKp46⁺ cells using a novel Ncr1^greenCre mouse strain: NK cells are essential for protection against pulmonary B16 metastases

et al. 2014

View full text Add to dashboard Cite

To study gene functions specifically in NKp46 + cells we developed novel Cre mice allowing for conditional gene targeting in cells expressing Ncr1 (encoding NKp46). We generated transgenic Ncr1 greenCre mice carrying an EGFPcre fusion under the control of a proximal Ncr1 promoter that faithfully directed EGFPcre expression to NKp46 + cells from lymphoid and nonlymphoid tissues. This approach allowed for direct detection of Cre-expressing NKp46 + cells via their GFP signature by flow cytometry and histology. Cre was functional as evidenced by the NKp46 + cell-specific expression of RFP in Ncr1 greenCre RosadtRFP reporter mice. We generated Ncr1 greenCre Il2rg fl/fl mice that lack NKp46 + cells in an otherwise intact hematopoietic environment. Il2rg encodes the common gamma chain (γ c ), which is an essential receptor subunit for cytokines (IL-2, -4, -7, -9, -15, and -21) that stimulate lymphocyte development and function. In Ncr1 greenCre Il2rg fl/fl mice, NK cells are severely reduced and the few remaining NKp46 + cells escaping γc deletion failed to express GFP. Using this new NK-cell-deficient model, we demonstrate that the homeostasis of NKp46 + cells from all tissues (including the recently described intraepithelial ILC1 subset) requires Il2rg. Eur. J. Immunol. 2014. 44: 3380-3391 Innate immunity 3381 in vivo and their capacity to promptly kill target cells (including tumors and infected cells) without prior sensitization [1][2][3]. NK cells have been shown to participate in immune responses to various microbial pathogens, including viruses, bacteria, and parasites (reviewed in [4]) through secretion of type 1 cytokines that recruit and activate hematopoietic effector cells. In the mouse, NK cells can be identified as CD3-NKp46 + cells that coexpress NK1.1 on appropriate genetic backgrounds (including C57BL/6). NK cells do not represent a homogeneous cell population but can be phenotypically separated into several subpopulations. Commonly used cell surface markers include CD27 and CD11b that divide NK-cell populations into CD27 + CD11b − NK cells (representing the least differentiated cells) that give rise to CD27 − CD11b + NK cells via CD27 + CD11b + NK-cell intermediates [5,6]. CD11b + NK cells can be further subdivided on the basis of KLRG1 expression with KLRG1 + marking terminally differentiated NK cells [7]. NK cells have been detected in lymphoid tissues, including bone marrow (BM), spleen, lymph nodes (LNs), Peyer's patches, and thymus, but also in nonlymphoid tissues, including liver, lungs, uterus, pancreas, skin, and intestine (reviewed in [8]).Many studies aiming at deciphering gene functions for NK cells make use of germ-line gene targeted mice where all cells lack the gene in question. Given that the activity and differentiation of NK cells is intimately regulated by other immune cells (reviewed in [9,10]), the consequences of gene deletions that intrinsically affect NK cells may be difficult to distinguish from indirect effects that occur in non-NK cells. Furthermore, studying the role of N...

show abstract

Section: Ablation Of Nk Cells By Generating Ncr1 Greencre Il2rg Fl/flmentioning

confidence: 99%

Conditional ablation of NKp46⁺ cells using a novel Ncr1^greenCre mouse strain: NK cells are essential for protection against pulmonary B16 metastases

et al. 2014

View full text Add to dashboard Cite

show abstract

“…IL-2Rb is constitutively expressed on resting T cells and is also a component of the IL-15 receptor (Grabstein et al 1994). The widespread expression of IL-2Rg on immune cells and its presence in several other interleukin receptor complexes (IL-4, IL-7, IL-9, IL-15, and IL-21) lead to the alternative name of common gamma chain (gc) (Sugamura et al 1996;Lai et al 1996;Kovanen and Leonard 2004;Alves et al 2007;Wang et al 2009). Receptor monomers bind IL-2 with a wide range of affinities (a = 10 nM, b = 100 nM, g~0.7 mM), while complexes exist as an intermediate affinity dimer (b-and g-subunits,~1 nM) and a high-affinity trimer (a-, b-, and g-subunits, K d~5 pM).…”

Section: Ligand and Receptor Biologymentioning

confidence: 99%

Small-Molecule Inhibitors of IL-2/IL-2R: Lessons Learned and Applied

Wilson

Arkin

2010

Current Topics in Microbiology and Immunology

View full text Add to dashboard Cite

“…IL-2 is a cytokine that exerts potent immunoregulatory effects upon effector and regulatory T cells, NK and NK-T cells (reviewed in [17]). The rationale for combining IL-2 and IL-12 therapies stems primarily from the fact that the two cytokines reciprocally upregulate each other's receptors and use separate signaling pathways to induce different but complementary biological effects.…”

Section: Il-2/il-12mentioning

confidence: 99%

Immunotherapy of cancer by IL-12-based cytokine combinations

Weiss

Subleski

Wigginton

et al. 2007

Expert Opinion on Biological Therapy

203

121

View full text Add to dashboard Cite

Cancer is a multi-faceted disease comprising complex interactions between neoplastic and normal cells. Over the past decade, there has been considerable progress in defining the molecular, cellular and environmental contributions to the pathophysiology of tumor development. Despite these advances, the conventional treatment of patients still generally involves surgery, radiotherapy and/ or chemotherapy and the clinical outcome for many of these efforts remains unsatisfactory. Recent studies have highlighted the feasibility of using immunotherapeutic approaches that seek to enhance host immune responses to developing tumors. These strategies include immunomodulatory cytokines, with tumor necrosis factor (TNF) alpha, type I or type II Interferons (IFNs), Interleukins (IL)-2, IL-12, IL-15 and IL-18 being among the most potent inducers of anti-tumor activity in a variety of pre-clinical studies. More recently, some exciting new cytokines have been characterized, such as IL-21, IL-23, IL-27, and their immunomodulatory and anti-tumor effects in vitro and in vivo suggest that they may have considerable promise for future immunotherapy protocols. The promise of cytokine therapy does indeed derive from the identification of these novel cytokines, but even more fundamentally, the field is greatly benefiting from the ever-expanding amount of preclinical data that convincingly demonstrate synergistic and/or novel biological effects that may be achieved through the use of several combinations of cytokines with complementary immunestimulating capabilities. One cytokine in particular, IL-12, holds considerable promise by virtue of the fact that it plays a central role in regulating both innate and adaptive immune responses, can by itself induce potent anti-cancer effects, and synergizes with several other cytokines for increased immunoregulatory and anti-tumor activities. This review will discuss the anti-tumor activity of IL-12, with a special emphasis on its ability to synergize with other cytokines for enhancement of immune effector cell populations and regulation of host-tumor cell interactions and the overall tumor microenvironment.

show abstract

Common γ chain cytokines: Dissidence in the details

Cited by 60 publications

References 112 publications

Conditional ablation of NKp46⁺ cells using a novel Ncr1^greenCre mouse strain: NK cells are essential for protection against pulmonary B16 metastases

Conditional ablation of NKp46⁺ cells using a novel Ncr1^greenCre mouse strain: NK cells are essential for protection against pulmonary B16 metastases

Small-Molecule Inhibitors of IL-2/IL-2R: Lessons Learned and Applied

Immunotherapy of cancer by IL-12-based cytokine combinations

Contact Info

Product

Resources

About

Common γ chain cytokines: Dissidence in the details

Cited by 60 publications

References 112 publications

Conditional ablation of NKp46+ cells using a novel Ncr1greenCre mouse strain: NK cells are essential for protection against pulmonary B16 metastases

Conditional ablation of NKp46+ cells using a novel Ncr1greenCre mouse strain: NK cells are essential for protection against pulmonary B16 metastases

Small-Molecule Inhibitors of IL-2/IL-2R: Lessons Learned and Applied

Immunotherapy of cancer by IL-12-based cytokine combinations

Contact Info

Product

Resources

About

Conditional ablation of NKp46⁺ cells using a novel Ncr1^greenCre mouse strain: NK cells are essential for protection against pulmonary B16 metastases

Conditional ablation of NKp46⁺ cells using a novel Ncr1^greenCre mouse strain: NK cells are essential for protection against pulmonary B16 metastases