INT285489

Context Info Confidence 0.32 First Reported 2009 Last Reported 2010 Negated 4 Speculated 0 Reported most in Body Documents 9 Total Number 11 Disease Relevance 10.97 Pain Relevance 3.63

extracellular space (Il22) extracellular region (Il22)

Anatomy Link Frequency T cells 8 respiratory 6 fibroblast 2 lamina 2 skin 2 Il22 (Mus musculus)

Pain Link Frequency Relevance Heat cytokine 269 100.00 rheumatoid arthritis 383 99.96 Inflammation 302 99.84 Crohn's disease 11 99.32 psoriasis 273 98.32 chemokine 37 97.00 Arthritis 103 92.00 methotrexate 56 90.92 Inflammatory response 13 84.32 antagonist 11 53.92

Disease Link Frequency Relevance Heat Rheumatoid Arthritis 384 99.96 INFLAMMATION 308 99.84 Disease 285 99.32 Targeted Disruption 25 98.92 Infection 143 98.88 Psoriasis 330 98.32 Inflammatory Bowel Disease 21 97.74 Bacterial Respiratory Disease 2 97.56 Bacterial Infection 9 95.88 Acanthosis 8 93.16

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

In humans STAT3 represents one of the disease loci for Crohn's and inflammatory bowel disease (IBD) [99], and most likely relates to the capacity of Stat3 to promote intestinal barrier function and integrity in response to IL6, IL11 and IL22 exposure.

Positive_regulation (response) of Gene_expression (exposure) of IL22 in bowel associated with inflammatory bowel disease, inflammation and disease

1) Confidence 0.32 Published 2010 Journal Cell Div Section Body Doc Link PMC2887830 Disease Relevance 1.11 Pain Relevance 0.12

In RA, expression of IL-22 was found to be upregulated in synovium and capable of inducing synovial fibroblast proliferation and chemokine production [33].

Positive_regulation (upregulated) of Gene_expression (expression) of IL-22 in fibroblast associated with chemokine and rheumatoid arthritis

2) Confidence 0.26 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991017 Disease Relevance 1.06 Pain Relevance 0.67

IL-22 production by Th17 cells has been shown to be dependent upon IL-23 [38,45,46], thus our observation, which corroborates that of Shen et al. [25], that very few IL-17-producing CD4 T cells express IL-23R provides a potential explanation for the paucity of IL-22-positive IL-17-positive CD4 T cells we observed.

Positive_regulation (upon) of Gene_expression (production) of IL-22 in T cells

3) Confidence 0.19 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991017 Disease Relevance 0.74 Pain Relevance 0.40

Analysis of IL-22 and IL-23R expression on IL-17-positive CD4 T cells in PBMC and SFMC of patients with RA

Positive_regulation (on) of Gene_expression (expression) of IL-22 in T cells associated with rheumatoid arthritis

4) Confidence 0.19 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991017 Disease Relevance 0.39 Pain Relevance 0.38

Recently, a small subpopulation of skin-homing CD4+ T cells has been identified produced IL-22 as well but lack the production of IL-17 or IFN-?

Positive_regulation (homing) of Gene_expression (produced) of IL-22 in T cells

5) Confidence 0.14 Published 2010 Journal Journal of Allergy Section Body Doc Link PMC2957587 Disease Relevance 0.33 Pain Relevance 0.06

IL-22 is also increased in psoriatic lesions and in plasma and these levels correlate with disease severity.18 Multiple reports have also implicated the IL-23 dependent IL-22, but not IL-17 production, in protective immunity to infection with gram-negative organisms such as Salmonella enteritidis in the respiratory and digestive epithelium.19–21 Recently, a Th22 cell subpopulation (characterized by the secretion of IL-22 and TNF-?)

Neg (not) Positive_regulation (not) of Gene_expression (production) of IL-22 in respiratory associated with psoriasis, disease and infection

6) Confidence 0.12 Published 2010 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2857612 Disease Relevance 1.25 Pain Relevance 0.30

IL-22 is also increased in psoriatic lesions and in plasma and these levels correlate with disease severity.18 Multiple reports have also implicated the IL-23 dependent IL-22, but not IL-17 production, in protective immunity to infection with gram-negative organisms such as Salmonella enteritidis in the respiratory and digestive epithelium.19–21 Recently, a Th22 cell subpopulation (characterized by the secretion of IL-22 and TNF-?)

Neg (not) Positive_regulation (implicated) of Gene_expression (production) of IL-22 in respiratory associated with psoriasis, disease and infection

7) Confidence 0.12 Published 2010 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2857612 Disease Relevance 1.27 Pain Relevance 0.31

IL-22 is also increased in psoriatic lesions and in plasma and these levels correlate with disease severity.18 Multiple reports have also implicated the IL-23 dependent IL-22, but not IL-17 production, in protective immunity to infection with gram-negative organisms such as Salmonella enteritidis in the respiratory and digestive epithelium.19–21 Recently, a Th22 cell subpopulation (characterized by the secretion of IL-22 and TNF-?)

Neg (not) Positive_regulation (dependent) of Gene_expression (production) of IL-22 in respiratory associated with psoriasis, disease and infection

8) Confidence 0.12 Published 2010 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2857612 Disease Relevance 1.26 Pain Relevance 0.31

Further, it was demonstrated that psoriasis mediators IL-17 and IL-22 synergistically induce the production of IL-20 subfamily proteins in cultured human keratinocytes and the expression of the IL-22 receptor (IL-22R) was also increased in epidermal lesions versus normal skin.23 IL-17 and IL-22 coordinately enhanced cytokine, chemokine, and growth factor production depending on the amount of IL-22R expression.

Positive_regulation (increased) of Gene_expression (expression) of IL-22 in skin associated with chemokine, psoriasis and cytokine

9) Confidence 0.11 Published 2010 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2857612 Disease Relevance 0.95 Pain Relevance 0.46

In this study, splenocytes from DO11.10 T-cell antigen receptor (TCR) transgenic mice activated with ovalbumin peptide preferentially produced IL-22, but not the related cytokines, IL-19, IL-20 or IL-24, after IL-23 stimulation.

Positive_regulation (stimulation) of Neg (not) Gene_expression (produced) of IL-22 in T-cell associated with targeted disruption and cytokine

10) Confidence 0.11 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2768824 Disease Relevance 1.20 Pain Relevance 0.41

The colonization of the small intestine of mice with a single commensal microbe, such as segmented filamentous bacterium, was sufficient to induce the appearance of Th cells able to produce IL-17 and IL-22 in the lamina propria with related activation of inflammatory genes [75].

Positive_regulation (activation) of Gene_expression (produce) of IL-22 in lamina associated with inflammation

11) Confidence 0.04 Published 2010 Journal Journal of Biomedicine and Biotechnology Section Body Doc Link PMC2896618 Disease Relevance 1.43 Pain Relevance 0.21

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