cAMP responsive element modulator: a critical regulator of cytokine production

Rauen, Thomas; Hedrich, Christian M.; Tenbrock, Klaus; Tsokos, George C.

doi:10.1016/j.molmed.2013.02.001

Cited by 83 publications

(72 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TCR stimulation of cells from young animals resulted in lower numbers of DN T cells compared with T cells from diseased animals (p Ͻ 0.001). However, in both age groups, significantly more CD8 ϩ T cells (6 weeks, 9.15%, S. We demonstrated previously that the transcription factor CREM␣ is expressed at increased levels in T cells from SLE patients (28,29). After disease onset, MRL/lpr mice share key symptoms with SLE patients, including the enrichment of DN T cells and elevated T cell expression of CREM␣.…”

Section: A Subset Of Cd8mentioning

confidence: 62%

“…In both CD8 ϩ T cells from SLE patients and healthy controls, CREM␣ was recruited to CNS2 in response to T cell activation with anti-CD3 and anti-CD28 antibodies where it replaces CREB. Notably, SLE T cells showed enriched (28,29) CREM␣ recruitment to the CNS2 region, whereas CREB was less recruited to this site (Fig. 5D).…”

Section: A Subset Of Cd8mentioning

confidence: 99%

“…Transcriptional repression is mediated by the transcription factor cAMP-responsive element modulator ␣ (CREM␣), which is expressed at increased levels in T cells from SLE patients (28,29). CREM␣ exerts direct trans-repressing effects on a region syntenic to the murine CD8b promoter (6,30).…”

Section: Systemic Lupus Erythematosus (Sle)mentioning

confidence: 99%

“…CREM␣ Represses CD8 Gene Transcription-CREM␣ contributes to the dysregulation of cytokine expression and affects T cell subset distribution in SLE through transcriptional regulation of cytokines and the induction of epigenetic remodeling processes (28,(31)(32)(33)35). Thus, we asked whether CREM␣ also trans-regulates CD8 expression.…”

Section: A Subset Of Cd8mentioning

confidence: 99%

See 3 more Smart Citations

cAMP-responsive Element Modulator α (CREMα) trans-Represses the Transmembrane Glycoprotein CD8 and Contributes to the Generation of CD3+CD4−CD8− T Cells in Health and Disease

Hedrich

Rauen

Crispín

et al. 2013

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Section: A Subset Of Cd8mentioning

confidence: 62%

Section: A Subset Of Cd8mentioning

confidence: 99%

Section: Systemic Lupus Erythematosus (Sle)mentioning

confidence: 99%

Section: A Subset Of Cd8mentioning

confidence: 99%

See 2 more Smart Citations

cAMP-responsive Element Modulator α (CREMα) trans-Represses the Transmembrane Glycoprotein CD8 and Contributes to the Generation of CD3+CD4−CD8− T Cells in Health and Disease

Hedrich

Rauen

Crispín

et al. 2013

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

“…Increased IL-10 expression in SLE patients correlates with disease activity and antibody production, and IL-10 blockade corrected dysregulated cytokine responses (12) and mediated clinical improvement in a subset of SLE patients (13). Given the immune-regulatory effects of IL-10 on T cells, enhanced IL-10 expression in SLE is seemingly conflicting with the well-established overexpression of IL-6 and IL-17A in SLE (14)(15)(16). Recently, however, this contradiction has been at least partially resolved.…”

Section: Discussionmentioning

confidence: 99%

Stat3 promotes IL-10 expression in lupus T cells through trans- activation and chromatin remodeling

Hedrich

Rauen

Apostolidis

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

154

View full text Add to dashboard Cite

The immune-regulatory cytokine IL-10 plays a central role during innate and adaptive immune responses. IL-10 is elevated in the serum and tissues of patients with systemic lupus erythematosus (SLE), an autoimmune disorder characterized by autoantibody production, immune-complex formation, and altered cytokine expression. Because of its B cell-promoting effects, IL-10 may contribute to autoantibody production and tissue damage in SLE. We aimed to determine molecular events governing T cell-derived IL-10 expression in health and disease. We link reduced DNA methylation of the IL10 gene with increased recruitment of Stat family transcription factors. Stat3 and Stat5 recruitment to the IL10 promoter and an intronic enhancer regulate gene expression. Both Stat3 and Stat5 mediate trans-activation and epigenetic remodeling of IL10 through their interaction with the histone acetyltransferase p300. In T cells from SLE patients, activation of Stat3 is increased, resulting in enhanced recruitment to regulatory regions and competitive replacement of Stat5, subsequently promoting IL-10 expression. A complete understanding of the molecular events governing cytokine expression will provide new treatment options in autoimmune disorders, including SLE. The observation that altered activation of Stat3 influences IL-10 expression in T cells from SLE patients offers molecular targets in the search for novel target-directed treatment options.

show abstract

Heart and neural crest derivative 2‐induced preservation of sympathetic neurons attenuates sarcopenia with aging

Rodrigues

Wang

Messi

et al. 2020

J cachexia sarcopenia muscle

View full text Add to dashboard Cite

Background Sarcopenia, or age‐dependent decline in muscle force and power, impairs mobility, increasing the risk of falls, institutionalization, co‐morbidity, and premature death. The discovery of adrenoceptors, which mediate the effects of the sympathetic nervous system (SNS) neurotransmitter norepinephrine on specific tissues, sparked the development of sympathomimetics that have profound influence on skeletal muscle mass. However, chronic administration has serious side effects that preclude their use for muscle‐wasting conditions. Interventions that can adjust neurotransmitter release to changing physiological demands depend on understanding how the SNS affects neuromuscular transmission, muscle motor innervation, and muscle mass. Methods We examined age‐dependent expression of the heart and neural crest derivative 2 (Hand2), a critical transcription factor for SN maintenance, and we tested the possibility that inducing its expression exclusively in sympathetic neurons (SN) will prevent (i) motor denervation, (ii) impaired neuromuscular junction (NMJ) transmission, and (iii) loss of muscle mass and function in old mice. To test this hypothesis, we delivered a viral vector carrying Hand2 expression or an empty vector exclusively in SNs by vein injection in 16‐month‐old C57BL/6 mice that were sacrificed 6 months later. Techniques include RNA‐sequencing, real‐time PCR, genomic DNA methylation, viral vector construct, tissue immunohistochemistry, immunoblot, confocal microscopy, electrophysiology, and in vivo mouse physical performance. Results Hand2 expression declines throughout life, but inducing its expression increased (i) the number and size of SNs, (ii) muscle sympathetic innervation, (iii) muscle weight and force and whole‐body strength, (iv) myofiber size but not muscle fibre‐type composition, (v) NMJ transmission and nerve‐evoked muscle force, and (vi) motor innervation in old mice. Additionally, the SN controls a set of genes to reduce inflammation and to promote transcription factor activity, cell signalling, and synapse in the skeletal muscle. Hand2 DNA methylation may contribute, at least partially, to gene silencing. Conclusions Selective expression of Hand2 in the mouse SNs from middle age through old age increases muscle mass and force by (i) regulating skeletal muscle sympathetic and motor innervation; (ii) improving acetylcholine receptor stability and NMJ transmission; (iii) preventing inflammation and myofibrillar protein degradation; (iv) increasing autophagy; and (v) probably enhancing protein synthesis.

show abstract

cAMP responsive element modulator: a critical regulator of cytokine production

Cited by 83 publications

References 74 publications

cAMP-responsive Element Modulator α (CREMα) trans-Represses the Transmembrane Glycoprotein CD8 and Contributes to the Generation of CD3+CD4−CD8− T Cells in Health and Disease

cAMP-responsive Element Modulator α (CREMα) trans-Represses the Transmembrane Glycoprotein CD8 and Contributes to the Generation of CD3+CD4−CD8− T Cells in Health and Disease

Stat3 promotes IL-10 expression in lupus T cells through trans- activation and chromatin remodeling

Heart and neural crest derivative 2‐induced preservation of sympathetic neurons attenuates sarcopenia with aging

Contact Info

Product

Resources

About