ABDUL MALIK DINATA

200892459

INTRODUCTION

miRNA? TH2 cytokines? Asthma?

Non-coding RNA that blocks protein assembly by

binding to mRNA. Focus: miR-19a

miRNA

Th2
Cytokines

Asthma

IL-4, IL-5, IL-6, IL-9, IL-10, IL-13.

Focus: IL-4 and IL-13

Chronic inflammation of the airways

Character: airflow obstruction. bronchospasm.

miRNA?

Non-coding RNA with many targets due to imperfect base pairing with mRNA

miR17-92 cluster regulates the

differentiation and function of T cell subsets:
miR17 & 19b promotes TH1 and TH17 differentiation, inhibits Treg
miR 18a? miR19a? miR20a? miR92?

THIS PAPER BASICALLY TELLS US THAT

UPREGULATION OF MIR-19A
IN ASTHMA MAY BE AN
INDICATOR AND A CAUSE OF
INCREASED TH2 CYTOKINE
PRODUCTION IN THE
AIRWAYS

HOW?
MICE
in vitro; in vivo

HUMANS
qPCR

miR17-92 cluster promotes Th2 cytokine in

vitro
miR 17-92 cluster promotes type 2
inflammation in vivo

miRNA expression profiling in CD4+ T cells

from human asthmatic airways
miR19a >>>

Increase in T cell miR-19a expression in

humans with asthma may augment Th2 responses
in their airways

miR17-92 promotes Th2 cytokine

production
Th2 cytokines

miR17-92 deficient
= 17-92 delta

miR 17-92 sufficient

= 17-92 + (control)

miR 17-92
overexpression =

Th1 cytokines

17-92 tg

miR17-92 cluster
upregulates Th2 cytokine
production, no effect on
Th1, downregulates TNF
production

miR 17-92 cluster promotes type 2

inflammation in vivo

17-92 delta
OT-II Th2 cells
(no miR 17-92)

miR 17-92 cluster had a role in the in

vivo function of Th2 cells as inducers
of the allergic inflammatory
phenotype associated with asthma

17-92+ OT-II
Th2 cells (with
miR 17-92)

OT-II Th2 cells -transgenic Th2,

only expresses
MHC II

Organism -Cd28 -/- mice

qPCR profiling in human airway CD4+

mIR19a >>
Other miR 17-92 family:
miR 17, miR 18a, miR 19b, miR20a insignificant, miR 92a not detected.

miR17-92 Th2

MICE

cytokine >> type 2

allergic inflammation >>

Asthmatic subjects
have more miR19A

HUMANS

miR19A

- Candidate Th2
regulator

What this paper has

provide:

miR19A is a candidate
regulator of Th2
responses.

HOWEVER, larger studies

are needed to identify
correlations between
miR-19A expression and:

Asthma severity
Pulmonary function
Response to
corticosteroid treatment
Biomarkers of Th2
inflammation that stratify
asthma phenotypes

Is miR19a a novel drug target for

asthma?

Too early but not impossible

Animal model confirmed the concept of nasal miRNA

inhibitor therapy amelioration of allergic airway
inflammation

More research to understand the target networks:

NF-kB also plays a role in asthma and other allergy

miR155 might act as anti miR19A miR155 deficient T cells
tend to bias toward Th2 differentiation, miR deficient mice
develop asthma characteristic?
Other possible drivers of asthma pathogenesis?

CONCLUSION

Lets not be cruel

Information is accurate, all the key terms are well

defined.
Clear language, fair, logical and organised.
Hypo Normo Hyper
The author reminds us not to over-simplify the result,
however, they successfully convince us that

upregulation of miR-19a in asthma may

be an indicator and a cause of
increased th2 cytokine production in the
airways

Thank you!