Stat3protein & immunocompetent cells in psoriasis pathogenesis

STAT 3 Protein & Immuno Competent Cells in Psoriasis Pathogenesis M.YOUSRY ABDEL-MAWLA,MD Zagazig Faculty of Medicine,Egypt.

Signal transducers and activators of transcription ) Stat) Family ,[object Object],[object Object],[object Object]

Cytokines and growth factors that activate STAT proteins

Structure of STAT3 protein. ,[object Object]

STAT3 Activation ,[object Object],[object Object],[object Object]

Mechanism of Stat3 signaling ,[object Object]

Regulation of the STAT3 signal transduction pathway ,[object Object],[object Object],[object Object],[object Object]

Regulation of the STAT3 signal transduction pathway

Regulation of intracellular Stat3 signalling .

JAK/Stat pathway activation and inhibition. ,[object Object],[object Object],[object Object]

Small Molecule Inhibitors of Stat3 Signaling Pathway ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

Effects of STAT3 Deﬁciency on Cellular Function Stuart et al.T he Journal of Immunology, 2009, 182: 21–28

Psoriasis ,[object Object],[object Object]

Combined data on psoriasis susceptibility loci ,[object Object]

Psoriasis Clinical Presentation

Clinical Manifestations of Psoriasis

Histopathology of Psoriasis ,[object Object]

Immunopathology of Psoriasis ,[object Object],[object Object],[object Object],[object Object],[object Object]

Immunopathology of Psoriasis ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

[object Object],[object Object],[object Object],[object Object],[object Object]

[object Object],[object Object],[object Object]

Immunopathology of Psoriasis ( ( Nickoloff & Nestle : J Clin Invest 2004; 113: 1664–1675.).

Bidirectional flow of ‘information’ and cells in a mature psoriasis lesion ,[object Object],[object Object],[object Object]

Keratinocytes cross talks among immune cells in psoriasis

Psoriasis: Evidence of T-Cell Mediation ,[object Object],[object Object],[object Object],[object Object],[object Object]

T-Cell in Psoriasis ,[object Object],[object Object],[object Object]

T-Cell in Psoriasis ,[object Object],[object Object],[object Object],[object Object]

Serum IL17 & IL22 in psoriasis Inas Almakhzangy & A. Gaballa Egyptian Dermatology Online Journal 5 (1): 4, 2009

T Helper 1 versus 2 in psoriasis ,[object Object],[object Object],[object Object],[object Object]

PSORIASIS IS a TH17 DISEASE :A Hypothesis ,[object Object],[object Object],[object Object]

STAT3 REGULATION of CYTOKINE-MEDIATED GENERATION of TH 17 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

Keratinocytes cross talks with immune cells in psoriasis

T Helper 17 Activation Mechanisms in Psoriasis ,[object Object]

TH17 cells: effector cytokines and their function. ,[object Object],[object Object],[object Object]

Proinflammatory Effects of IL17

Roles of IL-23 on T Helper 17 cells in Chronic Inflammation in Psoriasis Adapted from Iwakura & Ishigame, J Clin Invest 116:1218-1222 (2006) Dendritic cell Macrophage IL-23 IL-12 Th1 Th17 IFN  IL-1, IL-6 TNF Inflammatory response Endothelial cells Stromal cells Epithelial cells Fibroblasts Macrophage IL-17, IL-6 IL-1 IL-6 IL-8 TNF IL-12R IL-23R IL-23R

Roles of IL-23 on T Helper 17 cells in Chronic Inflammation in Psoriasis ,[object Object],[object Object],[object Object]

Toll like Receptor (TLR) in Th17 -mediated Autoimmune Inflammation ( Goriely S, Neurath M, Goldman M, Nature Rev Immunol 2007 ) IL-23 IL-12 IL-27 TLR3 TLR2 Th1 Th1 Th17 IFN-  Autoimmune Inflammation polyI : C PGN IFN- 

The IL23 – IL17 axis: a critical role in autoimmune inflammation ,[object Object],[object Object],Cua et al., Nature 421:744, 2003 Weaver et al., Immunity 24:677, 2006 Mensah-Brown et al., Eur J Immunol 36:216, 2006 S Hue et al. J Exp Med 11:2473, 2006

Genetic Polymorphism ,[object Object],[object Object],[object Object]

Stat3 links activated keratinocytes and immunocytes required for development of psoriasis ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

A positive feedback mechanism for Th1/Th17 inflammation . ,[object Object],[object Object],[object Object]

[object Object],[object Object],[object Object],[object Object]

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Experimental Models of Psoriasis ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

Experimental Models of Psoriasis ,[object Object],[object Object],[object Object],[object Object]

Experimental Models of Psoriasis ,[object Object]

Up-regulated molecules in keratinocytes of K5.Stat3C mice ,[object Object]

Development of psoriasis following wound healing . ,[object Object]

Psoriatic lesions of K5.Stat3C mice ,[object Object]

A Tender Piece of Information

Do Other Therapies Work Within This Framework? ,[object Object],[object Object]

Studies on Stat 3 in Psoriasis

Psoriasis: New Immunologic Approaches to Treatment ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

Therapeutic Targets in Psoriasis As a T Helper 17 Cell-Mediated Disease

Anti TNF approved for psoriasis treatment JEADV 2010, 24 (Suppl. 5), 2–24

IL-12/IL-23 Inhibitors in Psoriasis ,[object Object],[object Object],[object Object]

IL-12/IL-23 as Therapeutic Targets in Psoriasis ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Reviewed in Torti et al., J Am Acad Dermatol, 2007 doi: 10.1016/j.jaad.2007.07.016

Effect of a single 5 mg/kg dose of anti-p40 mAb in psoriasis ,[object Object]

Current Rheumatology Reports 2007 , 9:461–467

Topical Macrolactam Ascomycin Analog( ABT-281 ) in Psoriasis ,[object Object],[object Object]

Future Psoriasis Therapy ( Wippel-Slupetzky&Stingl Curr Probl Dermatol., 2009, 38, : 172–189 )

IL-17A blocker & early promise for psoriasis ,[object Object],[object Object],[object Object],[object Object]

Message Home ,[object Object],[object Object],[object Object],[object Object]

Message Home ,[object Object],[object Object]

Stat3protein & immunocompetent cells in psoriasis pathogenesis

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Stat3protein & immunocompetent cells in psoriasis pathogenesis

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