Cloning of the human and murine interleukin-7 receptors: Demonstration of a soluble form and homology to a new receptor superfamily

Goodwin, Raymond G.; Friend, Della; Ziegler, Steven F.; Jerzy, R; Falk, Ben; Gimpel, Steven D.; Cosman, David; Dower, Steven K.; March, Carl J.; Namen, Anthony E.; Park, Linda

doi:10.1016/0092-8674(90)90342-c

Cited by 584 publications

(251 citation statements)

References 41 publications

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“…Its importance is illustrated by the fact that mice deficient for IL-7 (16) or IL-7R␣ (17) or humans with loss-of-function mutations in IL-7R␣ (18) have a marked deficiency in T cell development. The receptor for IL-7 is composed of the IL-7-specific subunit (IL-7R␣) (23) and ␥ c , the latter associating with the Janus kinase 3 (13,20,24,25). Mutations in ␥ c and Janus kinase 3 also result in a reduction in T cell number, and targeted mutations of other ␥ c -using cytokines (IL-2, IL-4, and IL-15) clearly indicate that IL-7 has nonredundant functions in lymphopoiesis (26 -30).…”

Section: Discussionmentioning

confidence: 99%

Positive Effects of Glucocorticoids on T Cell Function by Up-Regulation of IL-7 Receptor α

Franchimont

Galon

Vacchio

et al. 2002

The Journal of Immunology

145

102

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Despite the effects of glucocorticoids on immune function, relatively little is known about glucocorticoid-inducible genes and how their products may regulate lymphocyte function. Using DNA microarray technology to analyze gene expression in PBMC from healthy donors, we identified IL-7Rα as a glucocorticoid-inducible gene. This observation was confirmed at the mRNA and protein levels. Conversely, TCR signaling decreased IL-7Rα expression, and the relative strength of signaling between these two receptors determined the final IL-7Rα levels. The up-regulation of IL-7Rα by glucocorticoids was associated with enhanced IL-7-mediated signaling and function. Moreover, IL-7-mediated inhibition of apoptosis at increasing concentrations of glucocorticoids is consistent with enhanced cell sensitivity to IL-7 following glucocorticoid exposure. These observations provide a mechanism by which glucocorticoids may have a positive influence on T cell survival and function.

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Section: Discussionmentioning

confidence: 99%

Positive Effects of Glucocorticoids on T Cell Function by Up-Regulation of IL-7 Receptor α

Franchimont

Galon

Vacchio

et al. 2002

The Journal of Immunology

145

102

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“…It was recently shown that two of these latter residues are also important for activation of STAT1 (consensus sequence Tyr-Xaa-Pro-Gln) (Gerhartz et al, 1996). The box 3 motif is also found in the receptors for IL-7 (Goodwin et al, 1990), IL-9 (Renauld et al, 1992), IL-10 (Liu et al, 1994), and thrombopoietin (Vigon et al, 1992), in the OSMspecific receptor (OSMRP) (Mosley et al, 1996), and in the leptin receptor (OB-R) (Tartaglia et al, 1995). The OSMRP and the OB-R are related to gp130 in primary structure (23.3% and 20.7% overall amino acid identity, respectively) and in modular structure, featuring both Ig-like and FN III domains (Hibi et al, 1990;Tartaglia et al, 1995;Mosley et al, 1996).…”

Section: The Il-6 Signal Transduce< Gp130mentioning

confidence: 99%

Interleukin‐6: Structure‐function relationships

et al. 1997

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Interleukin-6 (IL-6) is a multifunctional cytokine that plays a central role in host defense due to its wide range of immune and hematopoietic activities and its potent ability to induce the acute phase response. Overexpression of IL-6 has been implicated in the pathology of a number of diseases including multiple myeloma, rheumatoid arthritis, Castleman's disease, psoriasis, and post-menopausal osteoporosis. Hence, selective antagonists of IL-6 action may offer therapeutic benefits. IL-6 is a member of the family of cytokines that includes interleukin-1 1, leukemia inhibitory factor, oncostatin M, cardiotrophin-1, and ciliary neurotrophic factor. Like the other members of this family, IL-6 induces growth or differentiation via a receptor-system that involves a specific receptor and the use of a shared signaling subunit, gp130. Identification of the regions of IL-6 that are involved in the interactions with the IL-6 receptor and gp130 is an important first step in the rational manipulation of the effects of this cytokine for therapeutic benefit. In this review, we focus on the sites on IL-6 which interact with its low-affhity specific receptor, the IL-6 receptor, and the high-affinity converter gp130. A tentative model for the IL-6 hexameric receptor ligand complex is presented and discussed with respect to the mechanism of action of the other members of the IL-6 family of cytokines.

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“…The cytokine IL-7, produced by stromal cells in both FL and BM, and its receptor play an essential role in the expansion of early B cells [1][2][3][4]. The receptor for IL-7 (IL-7R) comprises the IL-7Ra [5] and common gamma (c C ) chains [6]. It has been reported that BM B cell development is blocked at the generation of CD19 + cells in adult IL-7R -/-mice [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Impaired B‐1 and B‐2 B cell development and atypical splenic B cell structures in IL‐7 receptor‐deficient mice

et al. 2004

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The cytokine IL-7 and its receptor are essential for normal B and T lymphopoiesis. We have analyzed the role of this receptor in B cell development throughout ontogeny in IL-7 receptor a-deficient mice. We demonstrate that the IL-7 receptor becomes progressively more important with age. B lymphopoiesis takes place, albeit at reduced levels, in fetal liver and bone marrow of young mice, but is arrested in adults. The outcome is a severe reduction, from an early age, in peripheral B cells including follicular, marginal zone and B-1 B cells as well as perturbed splenic B cell structures, which are restored after adoptive transfer of normal spleen cells. We conclude that in the absence of the IL-7 receptor, the residual B lymphopoiesis occurring early in ontogeny must be facilitated by another component, whereas the IL-7 receptor is the key factor in adults. The impairment of marginal zone and B-1 B cells in IL-7 receptor-but not IL-7-deficient mice suggests non-redundant functions for the IL-7 receptor ligands, IL-7 and thymic stromal lymphopoietin.

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Cloning of the human and murine interleukin-7 receptors: Demonstration of a soluble form and homology to a new receptor superfamily

Cited by 584 publications

References 41 publications

Positive Effects of Glucocorticoids on T Cell Function by Up-Regulation of IL-7 Receptor α

Positive Effects of Glucocorticoids on T Cell Function by Up-Regulation of IL-7 Receptor α

Interleukin‐6: Structure‐function relationships

Impaired B‐1 and B‐2 B cell development and atypical splenic B cell structures in IL‐7 receptor‐deficient mice

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