GeneSet Information

Tier III GS75763 • Association of genes regulated by CSA with proinflammatory cells: identification of genes uniquely expressed in activated cells

DESCRIPTION:

Expression of IL-17 correlated best at day 14. Consistent with Fig. 4A, iNOS, part of the Tip-DC pathway, correlated best with long-term effects. Five genes appear among the top six in both analyses. They are highlighted in gray: IL-17, SERPINB3, S100A12 (Th17), iNOS (Tip-DC), IL-19 (other). Of the Th1 path- way, MX-1 is number 5 among the short-term effects and IL-8 is number 3 among the long-term effects.

LABEL:

Genes Reg. by CSA

SCORE TYPE:

DATE ADDED:

2010-07-06

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

Haider AS, Lowes MA, Surez-Farias M, Zaba LC, Cardinale I, Khatcherian A, Novitskaya I, Wittkowski KM, Krueger JG

TITLE:

Identification of cellular pathways of "type 1," Th17 T cells, and TNF- and inducible nitric oxide synthase-producing dendritic cells in autoimmune inflammation through pharmacogenomic study of cyclosporine A in psoriasis.

JOURNAL:

Journal of immunology (Baltimore, Md. : 1950) Feb 2008, Vol 180, pp. 1913-20

ABSTRACT:

Therapeutic modulation of psoriasis with targeted immunosuppressive agents defines inflammatory genes associated with disease activity and may be extrapolated to a wide range of autoimmune diseases. Cyclosporine A (CSA) is considered a \"gold standard\" therapy for moderate-to-severe psoriasis. We conducted a clinical trial with CSA and analyzed the treatment outcome in blood and skin of 11 responding patients. In the skin, as expected, CSA modulated genes from activated T cells and the \"type 1\" pathway (p40, IFN-gamma, and STAT-1-regulated genes). However, CSA also modulated genes from the newly described Th17 pathway (IL-17, IL-22, and downstream genes S100A12, DEFB-2, IL-1beta, SEPRINB3, LCN2, and CCL20). CSA also affected dendritic cells, reducing TNF and inducible NO synthase (products of inflammatory TNF- and inducible NO synthase-producing dendritic cells), CD83, and IL-23p19. We detected 220 early response genes (day 14 posttreatment) that were down-regulated by CSA. We classified >95% into proinflammatory or skin resident cells. More myeloid-derived than activated T cell genes were modulated by CSA (54 myeloid genes compared with 11 lymphocyte genes), supporting the hypothesis that myeloid derived genes contribute to pathogenic inflammation in psoriasis. In circulating mononuclear leukocytes, in stark contrast, no inflammatory gene activity was detected. Thus, we have constructed a genomic signature of successful treatment of psoriasis which may serve as a reference to guide development of other new therapies. In addition, these data also identify new gene targets for therapeutic modulation and may be applied to wide range of autoimmune diseases. PUBMED: 18209089
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Annotation Information

No sequence read archive data associated with this GeneSet.


T-Lymphocytes (D013601)
Lymphocytes (D008214)
Tumor Necrosis Factor-alpha (D014409)
Immunoglobulins (D007136)
Antigens, CD3 (D017252)
Humans (D006801)
Interleukin-23 Subunit p19 (D053760)
Clinical Trial (D016430)
Psoriasis (D011565)
Dendritic Cells (D003713)
Patients (D010361)
Gene Expression Profiling (D020869)
Leukocytes, Mononuclear (D007963)
Leukocytes (D007962)
Skin (D012867)
Nitric Oxide Synthase Type II (D052247)
Antigens, CD (D015703)
Nitric Oxide Synthase (D019001)
Autoimmune Diseases (D001327)
Therapeutics (D013812)
Ficus (D030681)
Time (D013995)
Interleukin-8 (D016209)
Treatment Outcome (D016896)
Interleukin-2 Receptor alpha Subunit (D053645)
Inflammation (D007249)
Cells (D002477)
Blood (D001769)
Membrane Glycoproteins (D008562)
Gold (D006046)
T-Lymphocytes, Helper-Inducer (D006377)
Identification (Psychology) (D007062)
Nitric Oxide (D009569)
Cyclosporine (D016572)
Pharmacogenetics (D010597)
Signal Transduction (D015398)
Interleukin-17 (D020381)
Association (D001244)
Immunosuppressive Agents (D007166)
blood (MA:0000059)
skin (MA:0000151)
psoriasis (MP:0001193)
abnormal inflammatory response (MP:0001845)
cell (GO:0005623)

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Supported by NIH R01 AA18776 jointly funded by NIAAA and NIDA, and JAX Center for Precision Genetics NIH U54 OD 020351