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


�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.


�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


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)


Assay performance

Validation data of Bio-Plex Pro mouse Th17 Panel


Order information


On behalf of the Bio-Rad’s Bio-Plex Team, thank you for your attention.

th17 pathway research by bio-plex

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