Altered IL-4 mRNA Stability Correlates with Th1 and Th2 Bias and Susceptibility to Hypersensitivity Pneumonitis in Two Inbred Strains of Mice

Butler, Noah S.; Monick, Martha M.; Yarovinsky, Timur O.; Powers, Linda S.; Hunninghake, Gary W.

doi:10.4049/jimmunol.169.7.3700

Cited by 64 publications

(52 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is interesting to note that ROG also represses IL-4 gene activation in CD8 T cells (36). Thus, a genetic background in which ROG functions more efficiently may be expected to develop more frequent CD8 lineage T cells and to be more "Th1" prone as is the case for C57BL/6-based mice (20,37). Other transcription factors (9,38) or transcriptional repressors (11,39) also influence CD4/CD8 lineage decision.…”

Section: Discussionmentioning

confidence: 99%

Thymocyte-Intrinsic Genetic Factors Influence CD8 T Cell Lineage Commitment and Affect Selection of a Tumor-Reactive TCR

Shanker

Auphan-Anezin

Chomez

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

Selection of immature CD4CD8 double-positive (DP) thymocytes for CD4 or CD8-lineage commitment is controlled by the interaction of the TCR with stromal cell-expressed peptide/MHC. We show that thymocyte-intrinsic genes influence the pattern of expression of a MHC class I-restricted transgenic (tg) TCR so that in DBA/2 mice, DP thymocytes with a characteristically high expression of tg TCR, infrequently transit to CD8 single-positive thymocytes. In contrast, in B10.D2 mice, the same tg TCR is expressed at lower levels on a subpopulation of DP thymocytes that more frequently transit to CD8 single-positive thymocytes. These characteristics were not influenced by thymic stromal components that control positive selection. Radiation chimeras reconstituted with a mixture of BM from tg TCR mice of the two genetic backgrounds revealed that the relative frequency of transit to the CD8 lineage remained thymocyte-intrinsic. Identifying the gene products whose polymorphism controls CD8 T cell development may shed new light on the mechanisms controlling T cell commitment/selection in mice other than the most studied “C57BL/6”-based strains.

show abstract

Section: Discussionmentioning

confidence: 99%

Thymocyte-Intrinsic Genetic Factors Influence CD8 T Cell Lineage Commitment and Affect Selection of a Tumor-Reactive TCR

Shanker

Auphan-Anezin

Chomez

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…When the Th1/Th2 balance moves towards a Th1 response, the pathology seems to be more severe. C57Bl/6 mice are more susceptible to HP than other mice strains because they have decreased mRNA stability of Th2 cytokines leading to a Th1 response (122).…”

Section: Soluble Factorsmentioning

confidence: 99%

Hypersensitivity pneumonitis

Girard

and

Cormier

2009

Allergy

116

View full text Add to dashboard Cite

The first few cases of hypersensitivity pneumonitis (HP) were described in the early 20th century in farmers exposed to moldy hay or straw. As then, HP has been ascribed to multiple inhaled antigens found in a large variety of environmental settings. Hypersensitivity pneumonitis results from an exaggerated immune response, which gives rise to acute infection‐like symptoms or to progressive, sometimes irreversible lung damage. The diagnosis is based on a combination of clinical characteristics of the disease. Clinical diagnostic criteria have recently been published. The immune mechanisms leading to HP are still incompletely understood. Initially, believed to be a classes III and IV immune response, we now have a clearer understanding of the complex inflammatory events involved. These include the release of pro inflammatory cytokines and a decrease in the immune control mechanisms via surfactant, dendritic and T‐regulatory cells. Despite the improved understanding, the treatment and outcome of HP have not changed. Oral corticosteroids remain the only effective drugs and contact withdrawal constitutes the ideal solution. If unchecked, HP can lead to irreversible lung damage in the form of fibrosis or emphysema, respiratory insufficiency and even death.

show abstract

“…These findings indicate that GITR engagement on NKT cells contributes to HP attenuation in CD1d Ϫ/Ϫ mice. It is known that Th1 immune responses in vivo aggravate murine HP (31)(32)(33)(34)(35)(36). Therefore, we explored cytokine profiles in HP models by measuring the amount of IL-4, TGF-␤, and IFN-␥ in the lung tissues of wild-type B6, CD1d Ϫ/Ϫ mice and CD1d Ϫ/Ϫ mice adoptively transferred with control or DTA-1 treated NKT cells.…”

Section: Cd1dmentioning

confidence: 99%

Engagement of Glucocorticoid-Induced TNF Receptor Costimulates NKT Cell Activation In Vitro and In Vivo

Kim

et al. 2006

The Journal of Immunology

View full text Add to dashboard Cite

Glucocorticoid-induced TNF receptor (GITR) is known to provide costimulatory signals to CD4+CD25− and CD4+CD25+ T cells during immune responses in vivo. However, the functional roles of GITR expressed on NKT cells have not been well characterized. In this study, we have explored the functions of GITR as a costimulatory factor on NKT cells. GITR was found to be constitutively expressed on NKT cells and its expression was enhanced by TCR signals. GITR engagement using DTA-1, an agonistic mAb against GITR, in the presence of TCR signals, augmented IL-2 production, the expression of activation markers, cell cycle progression, and the nuclear translocations of NF-κB p50 and p65. Furthermore, GITR engagement enhanced the production of IL-4, IL-10, IL-13, and IFN-γ by NKT cells and the expression level of phosphorylated p65 in NKT cells in the presence of TCR engagement, indicating that GITR provides costimulatory signals to NKT cells. The costimulatory effects of GITR on NKT cells were comparable to those of CD28 in terms of cytokine production. Moreover, the coinjection of DTA-1 and α-galactosylceramide into B6 mice induced more IL-4 and IFN-γ production than the coinjection of control mAbs and α-galactosylceramide. In addition, the adoptive transfer of DTA-1-pretreated NKT cells into CD1d−/− mice attenuated hypersensitivity pneumonitis more than control IgG pretreated NKT cells in these mice. These findings demonstrate that GITR engagement on NKT cells modulates immune responses in hypersensitivity pneumonitis in vivo. Taken together, our findings suggest that GITR engagement costimulates NKT cells and contributes to the regulation of immune-associated disease processes in vivo.

show abstract

Altered IL-4 mRNA Stability Correlates with Th1 and Th2 Bias and Susceptibility to Hypersensitivity Pneumonitis in Two Inbred Strains of Mice

Cited by 64 publications

References 46 publications

Thymocyte-Intrinsic Genetic Factors Influence CD8 T Cell Lineage Commitment and Affect Selection of a Tumor-Reactive TCR

Thymocyte-Intrinsic Genetic Factors Influence CD8 T Cell Lineage Commitment and Affect Selection of a Tumor-Reactive TCR

Hypersensitivity pneumonitis

Engagement of Glucocorticoid-Induced TNF Receptor Costimulates NKT Cell Activation In Vitro and In Vivo

Contact Info

Product

Resources

About