IL‐27 paves different roads to Tr1

Vasanthakumar, Ajithkumar; Kallies, Axel

doi:10.1002/eji.201343479

Cited by 34 publications

(31 citation statements)

References 34 publications

(60 reference statements)

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“…13,[20][21][22] In mouse CD4 1 T cells, IL-6-associated signaling resulted in an evident increase of IL-10 mRNA levels in an IL-2-and IL-21-dependent pattern. 20 At the molecular level, IL-6 signaling drives expression of c-Maf, AhR, and IRF4, all of which are crucial transcription factors for IL-10 secretion and Tr1 cellular differentiation.…”

Section: Transcription Factors Associated With Tr1 Cellsmentioning

confidence: 99%

“…22 Stimulation of naive CD4 1 T cells in mice with IL-27 leads to phosphorylation of STAT3, which drives expression of B lymphocyte-induced maturation protein 1 (Blimp1) and Il10 genes via an Egr2-dependent pathway. 21 Iwasaki et al have reported that the transcription factor Egr-2 is required for Blimp-1-mediated IL-10 production in IL-27-activated Tr1 cells and in CD4…”

Section: Transcription Factors Associated With Tr1 Cellsmentioning

confidence: 99%

See 1 more Smart Citation

Type 1 regulatory T cells: a new mechanism of peripheral immune tolerance

et al. 2015

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Section: Transcription Factors Associated With Tr1 Cellsmentioning

confidence: 99%

Section: Transcription Factors Associated With Tr1 Cellsmentioning

confidence: 99%

Type 1 regulatory T cells: a new mechanism of peripheral immune tolerance

et al. 2015

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“…Supplementation of IL-27 Initiates Egr-2 Activation That Induces IL-10 Producing Tr1 Cells-IL-27 cytokine facilitates the differentiation of CD49, LAG3-expressing Tr1 regulatory cells, which execute their suppressor functions by secreting IL-10 anti-inflammatory cytokine (21). Studies have shown that the early growth response gene-2 (Egr-2), whose activation is initiated by IL-27, plays an important role in the differentiation of the CD49 ϩ LAG3 ϩ Tr1 subset and induction of IL-10 from these cells (21,22).…”

Section: Il-27 Treatment Inhibits Ovx-induced T Cell Proliferation Anmentioning

confidence: 99%

“…Studies have shown that the early growth response gene-2 (Egr-2), whose activation is initiated by IL-27, plays an important role in the differentiation of the CD49 ϩ LAG3 ϩ Tr1 subset and induction of IL-10 from these cells (21,22). Hence, transcript levels of Egr-2 were evaluated in CD4 ϩ T cells.…”

Section: Il-27 Treatment Inhibits Ovx-induced T Cell Proliferation Anmentioning

confidence: 99%

Interleukin 27 (IL-27) Alleviates Bone Loss in Estrogen-deficient Conditions by Induction of Early Growth Response-2 Gene

Shukla

Mansoori

Kakaji

et al. 2017

Journal of Biological Chemistry

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Edited by Xiao-Fan WangA growing understanding of the bone remodeling process suggests that inflammation significantly contributes to the pathogenesis of osteoporosis. T cells and various cytokines contribute majorly to the estrogen deficiency-induced bone loss. Recent studies have identified the IL-12 cytokine family as consisting of pro-inflammatory IL-12 and IL-23 and the anti-inflammatory IL-27 and IL-35 cytokines. IL-27 exerts protective effects in autoimmune diseases like experimental autoimmune encephalomyelitis; however, its role in the pathogenesis of osteoporosis remains to be determined. In this report, we study the effect of IL-27 supplementation on ovariectomized estrogen-deficient mice on various immune and skeletal parameters. IL-27 treatment in ovariectomized mice suppressed Th17 cell differentiation by inhibiting transcription factor ROR␥t. Supplementation of IL-27 activates Egr-2 to induce IL-10 producing Tr1 cells. IL-27 treatment prevented the loss of trabecular micro-architecture and preservedcorticalboneparameters.IL-27alsoinhibitedosteoblastapo-ptosis through increased Egr-2 expression, which induces antiapoptotic factors like MCL-1. IL-27 suppressed osteoclastogenesis in an Egr-2-dependent manner that up-regulates Id2, the repressor of the receptor activator of nuclear factor-B ligand-mediated osteoclastogenesis. Additionally, these results were corroborated in female osteoporotic subjects where we found decreased serum IL-27 levels along with reduced Egr-2 expression. Our study forms a strong basis for using humanized IL-27 toward the treatment of post-menopausal osteoporosis.

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“…Furthermore, the generation of Tr1 cells from peripheral CD4 + T cells has been shown to be greatly impaired in MS patients in comparison with healthy controls (52). Therefore, Tr1-mediated immunotherapy may be a potentially effective approach for the treatment of many autoimmune disorders, including inflammatory bowel disease or MS. Several groups have attempted to generate large numbers of Tr1 in vitro for clinical applications, and IL-27 is being considered currently to be an essential factor for the generation of Tr1 cells (53). In addition to IL-27, costimulatory signals through ICOS or CD46 play an important role in the generation or expansion of Tr1 cells.…”

Section: Discussionmentioning

confidence: 99%

CD26-Mediated Induction of EGR2 and IL-10 as Potential Regulatory Mechanism for CD26 Costimulatory Pathway

Hatano

Ohnuma

Otsuka

et al. 2015

The Journal of Immunology

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CD26 is associated with T cell signal transduction processes as a costimulatory molecule, and CD26+ T cells have been suggested to be involved in the pathophysiology of diverse autoimmune diseases. Although the cellular and molecular mechanisms involved in CD26-mediated T cell activation have been extensively evaluated by our group and others, potential negative feedback mechanisms to regulate CD26-mediated activation still remain to be elucidated. In the present study, we examine the expression of inhibitory molecules induced via CD26-mediated costimulation. We show that coengagement of CD3 and CD26 induces preferential production of IL-10 in human CD4+ T cells, mediated through NFAT and Raf-MEK-ERK pathways. A high level of early growth response 2 (EGR2) is also induced following CD26 costimulation, possibly via NFAT and AP-1–mediated signaling, and knockdown of EGR2 leads to decreased IL-10 production. Furthermore, CD3/CD26-stimulated CD4+ T cells clearly suppress proliferative activity and effector cytokine production of bystander T cells in an IL-10–dependent manner. Taken together, our data suggest that robust CD26 costimulatory signaling induces preferential expression of EGR2 and IL-10 as a potential mechanism for regulating CD26-mediated activation.

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IL‐27 paves different roads to Tr1

Cited by 34 publications

References 34 publications

Type 1 regulatory T cells: a new mechanism of peripheral immune tolerance

Type 1 regulatory T cells: a new mechanism of peripheral immune tolerance

Interleukin 27 (IL-27) Alleviates Bone Loss in Estrogen-deficient Conditions by Induction of Early Growth Response-2 Gene

CD26-Mediated Induction of EGR2 and IL-10 as Potential Regulatory Mechanism for CD26 Costimulatory Pathway

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