Isoform-specific inhibition of RORα-mediated transcriptional activation by human FOXP3

Du, Jun; Huang, Chun-Wei; Zhou, Baohua; Ziegler, SF

doi:10.4049/jimmunol.0990013

Cited by 70 publications

(93 citation statements)

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“…A similar physical interaction was first demonstrated between Foxp3 and RORa, which is closely related to RORgt and is similarly sufficient for inducing IL-17 expression but has only a minor redundant role in Th17 cell differentiation (Du et al, 2008;Yang et al, 2008b; L.Z. and D.R.L., unpublished data).…”

Section: Relationship Between Th17 and Th1-th2 Cellssupporting

confidence: 62%

Plasticity of CD4+ T Cell Lineage Differentiation

2009

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The differentiation of naive CD4(+) T cells into lineages with distinct effector functions has been considered to be an irreversible event. T helper type 1 (Th1) cells stably express IFN-gamma, whereas Th2 cells express IL-4. The discovery and investigation of two other CD4(+) T cell subsets, induced regulatory T (iTreg) cells and Th17 cells, has led to a rethinking of the notion that helper T cell subsets represent irreversibly differentiated endpoints. Accumulating evidence suggests that CD4(+) T cells, particularly iTreg and Th17 cells, are more plastic than previously appreciated. It appears that expression of Foxp3 by iTreg cells or IL-17 by Th17 cells may not be stable and that there is a great degree of flexibility in their differentiation options. Here, we will discuss recent findings that demonstrate the plasticity of CD4(+) T cell differentiation and the biological implications of this flexibility.

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Section: Relationship Between Th17 and Th1-th2 Cellssupporting

confidence: 62%

Plasticity of CD4+ T Cell Lineage Differentiation

2009

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“…Thus, K562-based aAPCs constructed to generate TGF-, IL-1-, IL-6, IL-21, and IL-23 might profoundly bolster the expansion and functionality of human Th17 cells. Alternatively, human CD4+ T cells can be transduced with the transcription factor RORC or RORA to confer Th17 function [72] and, perhaps, expanded with "Th17 aAPCs" to sustain their long-term growth.…”

Section: Expanding Human Th1 Th2 Th17 Cells With Aapcsmentioning

confidence: 99%

Adoptive immunotherapy: good habits instilled at youth have long-term benefits

et al. 2008

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Many recent advances in basic cell biology and immunology are a harbinger of progress in adoptive cell therapy (ACT) including (1) the finding that host lymphodepletion enhances engraftment and efficacy, (2) the recognition that in vitro T cell functions may not correlate with in vivo efficacy, and (3) the development of advanced ex vivo culture methods to expand lymphocytes to therapeutically effective numbers. In this article, we focus on the development of artificial antigen presenting cells (aAPCs) in our laboratory and their applicability to augment ACT protocols. We also describe how aAPCs can be used to broaden ACT to treat patients with a wide variety of cancers, chronic infectious diseases, and autoimmune manifestations.

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“…Two isoforms of FOXP3 proteins have been found in humans, namely FOXP3a and FOXP3b [12,22,23]. FOXP3b lacks exon 2 encoding region which is critical for its association with transcription factors ROR [24] and ROR t [25]. A range of FOXP3 mutations causing IPEX or involved in breast cancer have been extensively mapped over each functional domain encoding sequence [16,23].…”

Section: An Overview Of Foxp3 Subdomainsmentioning

confidence: 99%

“…FOXP3 may also physically interact with retinoic acid receptor (RAR)-related orphan receptor (ROR) family transcription factors including ROR t and ROR [24,25,40]. As a subfamily member of nuclear receptors, the thymus-speciWc expressing isoform, ROR t, is critical for the development and function of Th17 cells [41,42].…”

Section: Foxp3 Interacts With Ror T Through Exon 2 Regionmentioning

confidence: 99%

“…Moreover, Yang et al have found that another subfamily member of ROR proteins, ROR 4, also expressed in Th17 cells may cooperate with ROR t in the regulation of Th17 diVerentiation [43]. Full length FOXP3, but not the short isoform lacking exon 2 interacts with ROR and inhibits RORmediated transcriptional activation [24]. This interaction is dependent on the LxxLL motif within the exon 2 encoding region of FOXP3, but not on the forkhead domain.…”

Section: Foxp3 Interacts With Ror T Through Exon 2 Regionmentioning

confidence: 99%

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FOXP3 and its partners: structural and biochemical insights into the regulation of FOXP3 activity

Zhou

Song

et al. 2008

Immunol Res

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Forkhead box protein P3 (FOXP3) contributes to a unique transcriptional signature and serves as a functional marker of CD4(+)CD25(+) natural regulatory T cells. Dysfunction of FOXP3 in human is associated with fatal autoimmune disease known as immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) or X-linked autoimmunity-allergic disregulation syndrome (XLAAD). FOXP3 also can act as a breast tumor suppressor of the v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog (avian)) (Her2/neu) gene. While the suppressive functions of FOXP3 in maintaining the immune balance between tolerance and autoimmunity are obvious, the underlying molecular mechanism remains almost entirely undefined. Recent studies indicate that FOXP3 may form a dynamic superamolecular complex with a variety of molecular partners including transcription factors and enzymatic proteins to regulate transcription. How the FOXP3 ensemble changes in response to T-cell receptor signals and/or proinflammatory signal remains unclear although work from this laboratory has revealed its complexity. Structural information on FOXP3 complex may offer novel functional insights, as well as facilitate the development of rational means to modulate regulatory T-cell function in various human diseases.

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Isoform-specific inhibition of RORα-mediated transcriptional activation by human FOXP3

Abstract: This information is current as human FOXP3-mediated transcriptional activation by α Isoform-specific inhibition of ROR

Cited by 70 publications

References 0 publications

Plasticity of CD4+ T Cell Lineage Differentiation

Plasticity of CD4+ T Cell Lineage Differentiation

Adoptive immunotherapy: good habits instilled at youth have long-term benefits

FOXP3 and its partners: structural and biochemical insights into the regulation of FOXP3 activity

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