Th17 Pathway Research by Bio-plex
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Transcript of Th17 Pathway Research by Bio-plex
2011年6月28日星期二
Th17 Pathway Research By Bio-Plex
Zhiyang Shen, Senior Product Manager
Bio-Rad Laboratories, Inc
Alexandre S Basso et al. Cell Research , Vol 19 No 4 , April 2009
Timeline: advances on T helper research. Figure depicts some of the
most relevant findings in the field of T helper research
T helper cell research
Th17 Cytokine Pathway
The Th17 Cytokine Pathway is
‘au current’
• The importance of the Th17 cytokine
pathway in many diseases is a recent
discovery (in the last 5 years).
• Researchers are studying this group of
cytokines to understand immune system
function in numerous diseases, especially
autoimmune diseases, as summarized in
the adjacent table.
• The Th17 pathway is also a new area of
focus for the study of the body’s response
to other inflammatory conditions such as
those arising from conditions noted in the
table.
Traumatic Injury
Cardiovascular Disease
HIV Status
Parasitic Infection
Viral Infection
Bacterial Infection
Organ/tissue Transplantation
Rejection
Smoking
Th17 pathway implicated in
response to Inflammatory
Conditions related to:
Diabetes (Type 1)
Crohn’s Disease
Lupus
Lung Disease
Psoriasis
Multiple Sclerosis (MS)
Rheumatoid Arthritis (RA)
Th17 pathway implicated in
Disease States, especially
Autoimmune Diseases
What is a Th17 cell?
• Th17 cells are a subclass of immune cells called T helper (Th) cells, which
are a type of white blood cell whose specific immunological purpose is to
directing the function of other immune cell types.
• Th17 cells are identified by the major cytokine they release: IL-17.
• Steps in the generation of Th17 cells. The activation of naïve T cells in the presence of TGF-b and IL-6 initiates the Th17 differentiation pathway.
Amit Awasthi and Vijay K. Kuchroo,International Immunology, Vol. 21,
No. 5, pp. 489–498
Th17 Cytokine Pathway
Th17 Pathway Coverage
Th17 Pathway Coverage
• Some cytokines regulate the production and
function of Th17 cells (positive and negative
regulators)
• Others are released by Th17 cells upon
activation.
• Others are further downstream in the Th17
pathway.
• The adjacent image shows the complex
interactions of cytokines with the Th17 cell
(center), and the release of cytokines from the
cell.
Typical symptoms: skin inflammation and even canker
Importance of Th17 pathway in Today’s Research
Multiple Sclerosis
Rheumatoid Arthritis
• A quick internet search reveals the recent explosion in
the study of Th17 cytokines.
• March 2011 YTD Google Scholar citations on
“Th17 cytokine”: >17,500
• Percentage of those citations from last 3 years: 85%
• Prominent research topics are represented on this slide.
Bacterial InfectionCrohn’s Disease
�Causes of activation of Th17 cell are under debating, especially the role of TGF- β1in Human
�What is the actual role of transcription factor – RORγt in the development of Th17 cell? And can it be developed to a therapeutic target?
�The Role of Treg and its mechanism
�Distinct or overlay roles of IL-17A and IL-17F?
�Any changes of Th17 pathway in various diseases. Can we discover some biomarkers or targets for diagnostic and therapeutic applications from differentiation between controls and some specific diseases.
�Th17 cell signaling transduction in various diseases. Is there any biomarkers or targets in cell signaling pathway?
… …
Profiling cytokines in
Th17 cell
�Discover mechanism,
�Find biomarkers and targets
Some scientists concerns on Th17 cell
Th17 cytokine biology in mouse and human::::
Tesmer et al Role of IL-17 in human immune responses
Some scientists concerns on Th17 cell
�Although the Th1/Th2 paradigm represented a strong experimental
and theoretical basis allowing significant advances in the immunology
field, it was proven insufficient to fully explain certain immunological
phenomena.
�However, we should not expect that adding one or two new T-cell
subsets will give us a complete picture. Rather a lot more layers of
complexity will be necessary to uncover the ways the adaptive immune
system swings between tolerance and effector responses.
Some scientists concerns on Th17 cell
�For Th17 cell, it also needs strong and proven experimental and
theoretical basis for mechanism discovery and medical applications.
TH-17 cells, like Treg cells, can be selected by self antigens in the thymus.
Differential roles of IL-17A and IL-17F
Th17 pathway and cancer
Miyahara et al. PNAS October 7, 2008 vol. 105 no. 40 15507
Miyahara et al. PNAS October 7, 2008 vol. 105 no. 40 15507
Th17 pathway and cancer
�Despite recent advances in our understanding of the differentiation and function of Th17
cells in humans , very little is known about their prevalence and regulation in human
cancer.
�Here, we report the presence of high percentages of Th17 cells that secrete
predominantly IL-17 in the ovarian cancer-infiltrating T cell population.
�Cytokine profile analysis revealed that tumor cells, tumor-derived fibroblasts, and
antigen presenting cells (APCs) secrete several key cytokines in the tumor
microenvironment.
�We found that IL-1 was a potent inducer of Th17 cell differentiation and expansion,
whereas IL-6 and IL-23 were capable of expanding memory Th17 cells.
�Here, we provide an insightful mechanism by which Th17 cells are generated and
regulated by cytokines secreted from tumor cells and their immune infiltrates.
Cytokine Profiling for asthma predictors
Bio-Plex Pro mouse Th17 panel
ICAM-1
IL-27p28
IL-25 (IL-17E)
SingleplexAssays, Group III
IL-31
IL-33
CD40LIL-1ββββ
MIP-3ααααTNF-αααα
IL-22IFN-γγγγ
TGF- ββββ3IL-21IL-10
TGF- ββββ2IL-23IL-17A
TGF- ββββ1IL-17FIL-6
TGF-ββββAssays
Panel B, Group III (8-plex)
Panel A, Group I
(6-plex)
Bio-Plex Pro mouse Th17 Panel
Th17 pathway
Validation data of Bio-Plex Pro mouse Th17 Panel
Bio-Plex Pro mouse Th17 Panel
Optimized assay working
ranges to measure
cytokines from “normal”
and “diseased” samples
LODs are quite
low, indicating very
sensitive assays.
Extremely precise
assays, as indicated by
low % Coefficient of
Variation (%CV)
Bio-Plex Pro mouse Th17 Panel
Assay performance
Validation data of Bio-Plex Pro mouse Th17 Panel
Bio-Plex Pro mouse Th17 Panel
Order information
Bio-Plex Pro mouse Th17 Panel
On behalf of the Bio-Rad’s Bio-Plex Team, thank you for your attention.