Cytokines Flashcards
What T-helper type is involved in the pathogenesis of CAD?
Likely up regulation of a mix of Th1, Th2, Th17, and Th22
What cytokine is in the nucleus of cells?
IL-33, nuclear protein in epithelial tissues of various organs including lung, stomach, and skin
Where does IL-33 bind?
IL-1 receptor family ST2 (suppression of tumorigenicity 2)
How does IL-33 function as an alarmin?
released extracellularly upon tissue damage and cell death or stress and functions as endogenous danger signal
How can IL-33 further enhance allergic inflammation?
Released in full length already active but can also be processed by inflammatory proteases into shorter “hyperactive” mature form to further enhance allergic inflammation
IL-33 in CAD skin…
higher IL-33 in chronic lesional skin and excoriated skin
protein expression of IL-33 in keratinocytes, endothelial cells, and dermal infiltrating cells of AD skin
What is TSLP?
epithelial-derived cytokine, linking events at interfaces between body and environment to Th2 responses and development of allergic inflammation
What is CPEK?
canine progenitor epidermal keratinocyte line, may be a model for CAD skin
What are 2 receptors for house dust mite derived proteases and membrane proteins of Staph spp.?
PAR2 and TLR1/2
TSLP in CAD skin
CPEK stimulated by trypsin (PAR2 ligand) or synthetic triacylated lipopeptide (TLR1/2 ligand) shows upregulation of TSLP
skin of HDM-induced CAD model showed distinctive distribution pattern of TSLP (condensed staining pattern at stratum basale) compared to normal skin
CAD model showed down regulation of TSLP mRNA in skin after HDM exposure
= inconsistent results/insufficient evidence
CCL17/TARC
potent Th2 chemoattractant via CCR4 selectively expressed on Th2 cells
CCL17/TARC in CAD
CCL17 produced by CPEK especially when co-cultured with PAR2 agonist, proposed essential for recruitment of Th2 to skin
up regulation of CCL17 mRNA in skin of CAD dogs
significant difference between CCL17 expression in health and lesional skin of CAD but not with nonlesional skin
human plasma/serum CCL17 correlates with disease severity (biomarker for AD)
serum CCL17 moderate correlation with CADESI and levels reduced after treatment with steroids/oclacitinib, supports essential role
healthy control outlier had 10fold higher CCL17 and subsequently developed CAD, may suggest CCL17 can become elevated before onset of CAD
CCL22/MDC
another ligand for CCR4, can recruit Th2 to inflammatory loci of AD skin
CCL22/MDC in CAD
up regulation of CCL22 in lesional and nonlesional skin of AD dogs compared to healthy
positive correlation with pVAS and CADESI, may be essential in pathogenesis of Th2 dominated CAD lesions
unregulated mRNA of CCL22/MDC in AD skin compared to control
IL-4
one of the most important Th2 cytokines
Th2, mast cells, eosinophils, and basophils
IgE class switching of B cells and Th2 mediated immune responses
