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

Jiang, Qiong; Huang, Jiaqiang; Li, Wen Qing; Cavinato, Tiziana; Keller, Jonathan R.; Durum, Scott K.

doi:10.4049/jimmunol.178.1.228

Cited by 11 publications

(5 citation statements)

References 42 publications

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“…Moreover, almost all naïve cells also expressed CD127, the IL-7 receptor ␣ chain, which is strongly associated with the capacity of the cell to survive in the periphery. 38 These data, the explanation of which remains difficult, could however indicate that in DS an attempt takes place to maintain a constant number of immune cells in DS, possibly by means of persistent low degree of T cell activation. It is known that homeostatic expansion of naïve cells results in the acquisition of phenotypic and functional properties of memory cells, without transition through the typical effector intermediate.…”

Section: Analysis Of T Cell Differentiationmentioning

confidence: 91%

Homeostatic Cytokines and Expansion of Regulatory T Cells Accompany Thymic Impairment in Children with Down Syndrome

Roat

Prada

Lugli

et al. 2008

Rejuvenation Research

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Down syndrome (DS), the most common chromosomal abnormality in humans, is characterized by precocious immunologic aging that results, among other things, in alterations of B and T lymphocyte subsets and natural killer cells, defective phagocytosis, and chemotaxis of polymorphonuclear leukocytes. We studied 30 children affected by DS, compared them to 29 healthy controls, and evaluated the functionality of the thymus (by measuring the amount of lymphocytes that express the signal-joint T cell receptor rearrangement excision circles [sj-TREC+]), the plasma levels of interleukin (IL)-7 and IL-15, the proliferative T cell response to these cytokines, the expression of the alpha chain of the IL-7 receptor (CD127), the extrathymic differentiation of T lymphocytes, and the presence of natural regulatory T cells (Tregs) in peripheral blood. We found that DS children had a significantly lower number of sj-TREC+ lymphocytes, the levels of which were strongly correlated with age. We found higher plasma levels of IL-7 and IL-15 than in healthy controls, and a higher proliferative T cell response to IL-15. DS children also showed a lower percentage of CD4(+) cells and profound alterations of T cell differentiation, along with increased amount of Tregs and of cells expressing markers of apoptosis. We can thus hypothesize that the precocious thymic involution occurring in DS is mirrored by a high production of IL-7 and IL-15, which is crucial for cell survival and proliferation. The complex alterations present in the periphery are likely the result of a compensatory mechanism: the overproduction of homeostatic cytokines could be a reaction to the impaired intrathymic production of T lymphocytes and/or to the expansion of Treg in the periphery, and could be required to allow the survival of T cells.

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Section: Analysis Of T Cell Differentiationmentioning

confidence: 91%

Homeostatic Cytokines and Expansion of Regulatory T Cells Accompany Thymic Impairment in Children with Down Syndrome

Roat

Prada

Lugli

et al. 2008

Rejuvenation Research

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“…The dramatic reduction of thymic cellularity in mice with an engineered mutation of tyrosine 449 to phenylalanine 449 (Y449F) documents the importance of this single residue as well as the importance of the IL-7Rα chain itself [36]. Nonetheless, the IL-7Rα chain is not unique in promoting thymocyte development as domain-swapping experiments with intracellular regions of IL-4Rα, IL-9Rα, and the prolactin receptor partially replaced IL-7Rα function for αβ T cell development [37]. Interestingly, while all these different intracellular domains induced significant reconstitution of thymic T cell development, none of them were able to quantitatively restore T cell development to the extent of a native IL-7Rα chain.…”

Section: Il-7 Signaling and Il-7 Receptor Expression In Thymocytesmentioning

confidence: 99%

“…Interestingly, while all these different intracellular domains induced significant reconstitution of thymic T cell development, none of them were able to quantitatively restore T cell development to the extent of a native IL-7Rα chain. Additionally, none of them could restore γδ T cell generation in an IL-7Rα deficient thymus, suggesting that IL-7Rα specific signals regulate T cell development in both a quantitative and a qualitative manner [37]. Collectively, IL-7Rα plays an important role in IL-7 specific signaling as it recruits downstream signaling molecules through its Tyr 449 residue to induce survival, proliferation and differentiation.…”

Section: Il-7 Signaling and Il-7 Receptor Expression In Thymocytesmentioning

confidence: 99%

Intrathymic IL-7: The where, when, and why of IL-7 signaling during T cell development

Hong¹,

Luckey

Park

2012

Seminars in Immunology

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The thymus is the birthplace of all T lineage cells. But the thymus is also a cradle as it provides the environment for further maturation and differentiation of immature thymocytes. While many factors contribute to make the thymus a unique place for T cell development, here we review the essential role of intrathymic interleukin-7 (IL-7). In the absence of IL-7 signaling, survival, proliferation and differentiation of immature thymocytes are all severely impaired. Consequently, IL-7 is critical to nurture and guide T precursor cells through the diverse steps of thymic maturation. Interestingly, even as IL-7 signaling is such a critical factor, IL-7 signaling must be also actively suppressed during specific stages of T cell differentiation. These contradictory observations are puzzling but can be satisfactorily explained when understanding the developmental context of IL-7 signaling. In this regard, here we will discuss the spatiotemporal expression of intrathymic IL-7 and address the stage-specific effects of IL-7 signaling in developing thymocytes. Specifically, we will review other facets of intrathymic IL-7 beyond its role as a pro-survival factor and so clarify and reaffirm the unique role of IL-7 as a prime factor in T cell development and differentiation.

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“…IL‐7 receptor is made up of a heterodimer consisting of two subunits, the IL‐7R α chain and the γc chain. It is involved in the regulation of IL‐7 signaling pathway (Rose et al, ), which plays an important role in the growth, reproduction and differentiation of immature thymus cells, and acts as an irreplaceable decisive role in maintaining the balance of T cells in human peripheral blood (Hong, Luckey, & Park, ; Jiang et al, ; Walsh, ). According to the binding state of IL‐7R , IL‐7R can be divided into membrane‐bound receptor ( mIL‐7R ) and soluble receptor ( sIL‐7R ).…”

Section: Discussionmentioning

confidence: 99%

IL‐7R gene polymorphisms among patients with rheumatoid arthritis: A case–control study

Bai

et al. 2019

Molec Gen & Gen Med

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Background Rheumatoid arthritis (RA) is the most common inflammatory disease which refers to bony erosions and joint destruction largely caused by genetic factors. Our study aimed to explore whether interleukin‐7 receptor ( IL‐7R ) gene polymorphisms influenced RA risk in the Han Chinese population. Methods Five single nucleotide polymorphisms (SNPs) in IL‐7R gene were successfully genotyped using Agena MassARRAY platform. The associations between IL‐7R polymorphisms and RA were evaluated by the Chi‐squared test, T test, genetic model analysis, and haplotype analysis. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) using logistic regression analysis. Results Rs969129 and rs6451231 in the IL‐7R gene were associated with an increased risk of RA in the allele model (OR = 1.25, 95% CI = 1.05–1.49, p = 0.013; OR = 1.23, 95% CI = 1.03–1.48, p = 0.023), respectively. In the genetic models, rs969129 and rs6451231 were associated with an increased risk of RA. After stratification analysis by age, rs969129 and rs6451231 were associated with an increased risk of RA in patients (age <54). After stratification analysis by gender, rs6451231 was associated with an increased risk of RA in males, while rs969129 was found to be associated with an elevated risk of RA in females. And there was a strong linkage disequilibrium among the four SNPs (rs969129, rs118137916, rs10053847, and rs6451231). Conclusion These results suggested rs969129 and rs6451231 in the IL‐7R gene were associated with an increased risk of RA in the Han Chinese population.

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

Cited by 11 publications

References 42 publications

Homeostatic Cytokines and Expansion of Regulatory T Cells Accompany Thymic Impairment in Children with Down Syndrome

Homeostatic Cytokines and Expansion of Regulatory T Cells Accompany Thymic Impairment in Children with Down Syndrome

Intrathymic IL-7: The where, when, and why of IL-7 signaling during T cell development

IL‐7R gene polymorphisms among patients with rheumatoid arthritis: A case–control study

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