INT169015

Context Info Confidence 0.60 First Reported 2005 Last Reported 2010 Negated 0 Speculated 1 Reported most in Body Documents 50 Total Number 54 Disease Relevance 33.18 Pain Relevance 8.40

growth (FOXP3) nucleus (FOXP3) intracellular (FOXP3) embryo development (FOXP3) protein complex (FOXP3) cytoplasm (FOXP3)

Anatomy Link Frequency T cells 12 regulatory T cells 7 iTregs 2 nTreg 1 regulatory T-cells 1 FOXP3 (Homo sapiens)

Pain Link Frequency Relevance Heat tolerance 346 100.00 cytokine 1036 99.54 Arthritis 261 98.56 agonist 36 98.08 corticosteroid 32 93.76 Inflammation 1107 93.60 Crohn's disease 121 93.20 Inflammatory response 32 89.28 Inflammatory marker 1 84.92 rheumatoid arthritis 507 84.88

Disease Link Frequency Relevance Heat Repression 46 100.00 Immune Reconstitution Inflammatory Syndrome 31 100.00 Inflammatory Bowel Disease 570 99.74 Disease 975 99.56 Adenocarcinoma 36 99.12 Skin Cancer 108 98.98 Juvenile Chronic Polyarthritis 221 98.56 Systemic Lupus Erythematosus 119 98.44 Acquired Immune Deficiency Syndrome Or Hiv Infection 80 98.44 Necrosis 72 98.24

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

FOXP3 expression is detectable in 40% of peripheral T cells in JIA patients.

Gene_expression (expression) of FOXP3 in T cells associated with arthritis

1) Confidence 0.60 Published 2008 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2727897 Disease Relevance 1.16 Pain Relevance 0.55

FoxP3 expression can be found in activated non-regulatory T cells [32-35].

Gene_expression (expression) of FoxP3 in regulatory T cells

2) Confidence 0.57 Published 2010 Journal J Transl Med Section Body Doc Link PMC2936306 Disease Relevance 0.15 Pain Relevance 0.03

Yan et al. found no difference in Foxp3 expression in CD4+CD25high regulatory T cells of SLE patients [134].

Gene_expression (expression) of Foxp3 in regulatory T cells associated with systemic lupus erythematosus

3) Confidence 0.53 Published 2008 Journal Pediatr Rheumatol Online J Section Body Doc Link PMC2633304 Disease Relevance 1.26 Pain Relevance 0.08

Opposite findings of increased Foxp3 expression in active disease were reported in one study of pediatric SLE [133].

Gene_expression (expression) of Foxp3 associated with systemic lupus erythematosus and disease

4) Confidence 0.53 Published 2008 Journal Pediatr Rheumatol Online J Section Body Doc Link PMC2633304 Disease Relevance 1.27 Pain Relevance 0.06

In another study of synovial CD4+CD25high regulatory T cells in persistent and extended oligoarticular JIA, Massa et al. demonstrated that certain epitopes of human HSP increase the frequency of CD4+CD25high regulatory T cells and induce Foxp3 expression [109].

Gene_expression (expression) of Foxp3 in regulatory T cells associated with arthritis

5) Confidence 0.53 Published 2008 Journal Pediatr Rheumatol Online J Section Body Doc Link PMC2633304 Disease Relevance 0.79 Pain Relevance 0.35

FoxP3 is preferentially and stably expressed in peripheral nTreg, even after proliferation [23,27].

Gene_expression (expressed) of FoxP3 in nTreg

6) Confidence 0.53 Published 2008 Journal Pediatr Rheumatol Online J Section Body Doc Link PMC2633304 Disease Relevance 0.16 Pain Relevance 0.04

Furthermore, we selected this particular marker of immune suppression because IL-2 has been shown to regulate FoxP3 expression in human CD4+CD25+ Tregs [48] by inducing STAT-3 binding of the first intron of the FoxP3 gene [20] and because STAT-3 inhibitors have been shown to inhibit Tregs [26,36].

Gene_expression (expression) of FoxP3

7) Confidence 0.53 Published 2009 Journal J Transl Med Section Body Doc Link PMC2777138 Disease Relevance 0.44 Pain Relevance 0.04

Rather in the presence of proinflammatory cytokines and low concentration of TGF-beta, RORgammat expression is further upregulated, whereas FoxP3 expression and function are inhibited.

Gene_expression (expression) of FoxP3 associated with cytokine

8) Confidence 0.50 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2821644 Disease Relevance 0.06 Pain Relevance 0.12

The novel population is usually referred to as T regulatory cells (Tregs) and it is characterized by the expression of FoxP3.

Gene_expression (expression) of FoxP3

9) Confidence 0.50 Published 2009 Journal Mediators of Inflammation Section Abstract Doc Link PMC2821644 Disease Relevance 0.24 Pain Relevance 0.11

Treg cells expressing FoxP3 and/or IL-10 have a role in the immune homeostasis of the gut [103].

Gene_expression (expressing) of FoxP3 in gut

10) Confidence 0.50 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2821644 Disease Relevance 1.01 Pain Relevance 0.13

Furthermore, ectopic FoxP3 expression can phenotypically convert effector T-cells to regulatory T-cells [43].

Gene_expression (expression) of FoxP3 in regulatory T-cells

11) Confidence 0.50 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2821644 Disease Relevance 0.45 Pain Relevance 0.12

Recent publication describes the expression of FoxP3 in pancreatic ductal adenocarcinoma cells, providing evidence that this could be an important tumor escape mechanism [84]. 10.

Gene_expression (expression) of FoxP3 associated with adenocarcinoma and cancer

12) Confidence 0.50 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2821644 Disease Relevance 1.60 Pain Relevance 0.05

In fact in the presence of TGF-beta, CD4+ T-cells express both RORgammat and FoxP3, but RORgammat function is antagonized by FoxP3.

Gene_expression (express) of FoxP3 in T-cells

13) Confidence 0.50 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2821644 Disease Relevance 0 Pain Relevance 0.09

Moreover, it appears that expression of FoxP3 by iTregs or IL-17 by TH17 cells may not be stable and that there is a great degree of flexibility in their differentiation options [5].

Gene_expression (expression) of FoxP3 in iTregs

14) Confidence 0.50 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2821644 Disease Relevance 0.72 Pain Relevance 0.30

Elias et al. have shown that all-trans retinoic acid (ATRA) and other agonists of the retinoic acid receptor alpha (RARalpha) inhibit the formation of TH17 cells and promote FoxP3 expression [95], while Benson et al. have reported that ATRA enhances Treg growth and differentiation [96].

Gene_expression (expression) of FoxP3 associated with agonist

15) Confidence 0.50 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2821644 Disease Relevance 0.74 Pain Relevance 0.16

The likelihood of 'normal' FOXP3+ gene and endotoxin-tolerance among IRIS non-developers – Why?

Gene_expression (non) of FOXP3 associated with immune reconstitution inflammatory syndrome and tolerance

16) Confidence 0.48 Published 2007 Journal AIDS Res Ther Section Body Doc Link PMC2216023 Disease Relevance 0.96 Pain Relevance 0.31

CTLA-4 is constitutively expressed on Tregs that express the transcriptional factor FoxP3.

Gene_expression (express) of factor FoxP3

17) Confidence 0.44 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2821644 Disease Relevance 0.44 Pain Relevance 0.12

Furthermore, nonsuppressive activated T effectors, increased in IBD mucosa, can express FoxP3 [112, 113].

Gene_expression (express) of FoxP3 associated with inflammatory bowel disease

18) Confidence 0.44 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2821644 Disease Relevance 0.50 Pain Relevance 0.22

Tregs are characterized by the expression of FoxP3 (Forkhead box P3), a transcriptional repression factor of the forkhead-winged helix family of transcription factors [16].

Gene_expression (expression) of Forkhead box P3 associated with repression

19) Confidence 0.44 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2821644 Disease Relevance 0.96 Pain Relevance 0.12

Moreover it has been demonstrated that a substantial percentage of Tregs had transient or unstable expression of the transcription factor FoxP3.

Gene_expression (expression) of factor FoxP3

20) Confidence 0.44 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2821644 Disease Relevance 0.09 Pain Relevance 0.17

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