Role of stat3 protein & thelper 17 cell in psoriasis development by yousry

Role of Signal Transducer &Activator of Transcription( STAT)-3 & T Helper (Th) 17 Cell in Psoriasis Development ,[object Object],[object Object]

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 .

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

Psoriasis ,[object Object],[object Object]

Psoriasis Clinical Presentation

Psoriasis as an immune disorder

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

T HELPER(TH) CELL DEVELOPMENT&DIFFERENTIATION: A BACKGROUND

T-helper-cell differentiation ,[object Object],[object Object]

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The Th1-Th2 Paradigm Naive T cell Dendritic cell TGF  IFN  IL-4 +IL-6 -IL-6 Th1 Tbet Th2 Gata 3 Th17 ROR  T aTreg FoxP3 IL-12R IL-12 IL-23R IL-23 Adapted from Reiner et al., Cell , 2007 Autoimmunity Inflammation Cancer Extracellular bacteria Allergy and asthma Systemic pathology Harmful role Counter regulation Parasitic worms Intracellular pathogens Protective role

The Fate of Immune Responses Depends on the Balance between Effector and Regulatory T cells T regulatory T effector

STAT3 & Th17/Treg developmental programs ,[object Object],[object Object],[object Object],[object Object]

STAT3 & Th17/Treg developmental programs

T helper cell precursors being skewed towards Th1, Th2, Th17 and T regulatory cell (Treg) phenotypes on the basis of the cytokine environment .

Cytokine signaling and transcription factors in the regulation of Th17 cell differentiation . ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

Microbial Antigens & Th 17 Response ,[object Object]

ACTIVATION of T h 17 &STAT3 ,[object Object],[object Object],[object Object]

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

PSORIASIS IS Th17 DISEASE :A Hypothesis ,[object Object],[object Object],[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 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

T Helper 17 Activation Mechanisms in Psoriasis

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

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

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

Studies on Stat 3 in Psoriasis

Therapeutic Targets in Psoriasis As a T Helper 17 Cell Disease

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

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

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

Role of stat3 protein & thelper 17 cell in psoriasis development by yousry

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Role of stat3 protein & thelper 17 cell in psoriasis development by yousry