Signals from the IL-9 Receptor Are Critical for the Early Stages of Human Intrathymic T Cell Development

Smedt, Magda De; Verhasselt, Bruno; Kerre, Tessa; Vanhecke, Dominique; Naessens, Evelien; Leclercq, Georges; Renauld, Jean‐Christophe; Snick, Jacques Van; Plum, Jean

doi:10.4049/jimmunol.164.4.1761

Cited by 32 publications

(26 citation statements)

References 38 publications

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“…Although initially described as a T cell growth factor, naive T cells do not respond to IL-9, but recent data suggest that it is a critical factor for the early stages of intrathymic T cell maturation from precursor cells (12). It was also reported that IL-9 exerts growthenhancing activity on bone marrow-derived murine mast cell (BMMC) lines (13,14).…”

Section: Il-9 and Il-13 Production By Activated Mast Cells Is Stronglmentioning

confidence: 99%

IL-9 and IL-13 Production by Activated Mast Cells Is Strongly Enhanced in the Presence of Lipopolysaccharide: NF-κB Is Decisively Involved in the Expression of IL-9

Stassen

Müller

Arnold

et al. 2001

The Journal of Immunology

139

100

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Mast cells, due to their ability to produce a large panel of mediators and cytokines, participate in a variety of processes in adaptive and innate immunity. Herein we report that in primary murine bone marrow-derived mast cells activated with ionomycin or IgE-Ag the bacterial endotoxin LPS strongly enhances the expression of IL-9 and IL-13, but not IL-4. This costimulatory effect of LPS is absent in activated mast cells derived from the LPS-hyporesponsive mouse strain BALB/c-LPSd, although in these cells the proinflammatory cytokine IL-1 can still substitute for LPS. The enhanced production of mast cell-derived IL-13 in the presence of IL-1 is a novel observation. Coactivation of mast cells with LPS leads to a synergistic activation of NF-κB, which is shown by an NF-κB-driven reporter gene construct. In the presence of an inhibitor of NF-κB activation, the production of IL-9 is strongly decreased, whereas the expression of IL-13 is hardly reduced, and that of IL-4 is not affected at all. NF-κB drives the expression of IL-9 via three NF-κB binding sites within the IL-9 promoter, which we characterize using gel shift analyses and reporter gene assays. In the light of recent reports that strongly support critical roles for IL-9 and IL-13 in allergic lung inflammation, our results emphasize the potential clinical importance of LPS as an enhancer of mast cell-derived IL-9 and IL-13 production in the course of inflammatory reactions and allergic diseases.

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Section: Il-9 and Il-13 Production By Activated Mast Cells Is Stronglmentioning

confidence: 99%

IL-9 and IL-13 Production by Activated Mast Cells Is Strongly Enhanced in the Presence of Lipopolysaccharide: NF-κB Is Decisively Involved in the Expression of IL-9

Stassen

Müller

Arnold

et al. 2001

The Journal of Immunology

139

100

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“…Thus, although we show that the IL-9R intracellular domain can mimic IL-7R in ␣␤ T cell development, the IL-9 pathway apparently is not operational in normal conditions, presumably for lack of ligand and/or receptor expression. There is a report that exogenously added IL-9 can promote human thymic development in vitro (29), which might suggest that the receptor is present but the ligand is unavailable. Whereas IL-7 is produced by thymic stromal cells, IL-9 is primarily produced by activated T cells that would make it generally unavailable to thymic progenitors.…”

Section: Discussionmentioning

confidence: 99%

Role of the Intracellular Domain of IL-7 Receptor in T Cell Development

Jiang

Huang

et al. 2007

The Journal of Immunology

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Signals from the IL-7R are uniquely required for T cell development and maintenance, despite the resemblance of IL-7R to other cytokine receptors and the apparent sharing of common signaling pathways. This unique requirement could either reflect unique expression of IL-7R or IL-7, or it could indicate that the IL-7R delivers unique signals. To determine whether the IL-7R provided unique signals, we exchanged its intracellular domain with that of other cytokine receptors: IL-4R, IL-9R, and prolactin receptor (PRLR). Chimeric receptors were used to reconstitute development of IL-7R−/− hemopoietic progenitors by transducing the receptors in retroviral vectors. Whereas IL-7R−/− thymocytes are arrested at the double-negative stage, IL-4R, IL-9R, or PRLR all imparted some progression to the double-positive stage. IL-4R and PRLR gave only small numbers of thymocytes, whereas IL-9R gave robust αβ T cell development and reconstitution of peripheral CD4 and CD8 cells, indicating that it can duplicate many of the functions of IL-7R. However, IL-9R failed to reconstitute rearrangement of the TCRγ locus or development of γδ T cells. Thus, the IL-7R signals required in the αβ T cell lineage (such as survival and proliferation) are not unique to this receptor, whereas rearrangement of the TCRγ locus may require a signal that is not shared by other receptors.

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“…The biological effects of IL-9 are mediated by the functional IL-9 receptor complex, that is composed of this protein as well as the IL-2 receptor gamma (IL-2RG), a common gamma subunit shared by the receptors of many different cytokines [7]. The activation of this receptor leads to the activation of various Janus kinases (JAK) and STAT proteins [8] which connect to different biological responses [6]. In GCA, IL-9R positivity was observed among endothelial cells of vessels distributed in the inflammatory infiltrates and neutrophils [20].…”

Section: Il-9 and Th9 Cells In Large-vessel Vasculitismentioning

confidence: 99%

“…IL-9 signals through a heterodimeric receptor composed by a specific IL-9 receptor chain (IL-9Ra) and the common g-chain (also known as IL2Rg) [8]. IL-9Ra is expressed on immune cells and its activation also promotes mast cell growth [8,9] and accumulation in inflamed tissues, innate lymphoid cells (ILC) survival and B cell immunoglobulin (Ig)E class-switch recombination [9][10][11] (Fig.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-9 and T helper type 9 cells in rheumatic diseases

Ciccia

Guggino

Ferrante

et al. 2016

Clinical and Experimental Immunology

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SummaryInterleukin (IL)-9 is a 28-30 kDa monomeric glycosylated polypeptide belonging to the IL-7/IL-9 family of proteins that bind to a composite receptor consisting of the private receptor IL-9R and the IL-2 receptor, gamma (IL-2RG), a common gamma subunit shared by the receptors of many different cytokines. The IL-9R is expressed widely and IL-9 impacts a number of effector cells, such as effector T cells, B cells, innate lymphoid cells, mast cells, polymorphonuclear cells, epithelial cells and smooth muscle cells, playing an important role in regulating inflammatory immunity. The critical role of IL-9 in promoting cellular and humoral immune responses makes it an important focus of potential therapeutic interventions. Recently, a defined subset of T helper type cells, Th9 cells, has been identified by the potent production of IL-9. The involvement of the Th9 cell subset has been described in many types of inflammatory diseases, namely atopic diseases, helminth infections, experimental autoimmune encephalomyelitis and ulcerative colitis. In this review, we summarize the IL-9 biological activities, highlighting roles for IL-9 and Th9 cells in rheumatoid and psoriatic arthritis, systemic vasculitis, systemic lupus erythematosus and systemic sclerosis.

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Signals from the IL-9 Receptor Are Critical for the Early Stages of Human Intrathymic T Cell Development

Cited by 32 publications

References 38 publications

IL-9 and IL-13 Production by Activated Mast Cells Is Strongly Enhanced in the Presence of Lipopolysaccharide: NF-κB Is Decisively Involved in the Expression of IL-9

IL-9 and IL-13 Production by Activated Mast Cells Is Strongly Enhanced in the Presence of Lipopolysaccharide: NF-κB Is Decisively Involved in the Expression of IL-9

Role of the Intracellular Domain of IL-7 Receptor in T Cell Development

Interleukin-9 and T helper type 9 cells in rheumatic diseases

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