Medicine, Nursing and Health Sciences Epigenetic regulation of group 2 innate lymphoid cell development and function Prof. Colby Zaph ([email protected], 03 9905 0783) www.zaphlab.com , @colbyzaph Department of Biochemistry and Molecular Biology
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Medicine, Nursing and Health Sciences
Epigenetic regulation of group 2 innate
lymphoid cell development and function
Prof. Colby Zaph ([email protected], 03 9905 0783)
www.zaphlab.com, @colbyzaph
Department of Biochemistry and Molecular Biology
2
Innate Lymphoid Cells
30th November 2015ASI 2015
Id2
RORγt
Gata3 RORα Gfi1 Tcf1
ILC2
ILC3
3
G9a is the primary H3K9 dimethyltransferase
30th November 2015ASI 2015
G9a-deficient mice do not develop past E9.5
Hematopoietic specific G9a-deficient mice are viable and
have no overt defects
H3K9me2 is a repressive mark for gene expression
4
G9a controls immature ILC2 development
30th November 2015ASI 2015
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Lin
eag
e
c-kit
c-k
it
Sca-1
CD
25
CD127
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104
0
20
40
60
80
100
ST2
G9afl/fl
Vav.G9a−/−
3.6
3.3
11.2
37.7 1.7
9.2
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3.7 9.2 14.4
CD4.G9a−/−
0.08
0
0.02
0.04
0.06
G9afl/fl
Vav.
G9a−/−
% im
ma
ture
IL
C2
(o
f C
D4
5+)
**
B
G9afl/fl
Vav.G9a− /−
5
G9a controls lung ILC2 development
30th November 2015ASI 2015
Lin
ea
ge CD90.2
CD
25
CD127
G9afl/fl
Vav.G9a− /−
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104
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0
20
40
60
80
100
ST20.74
0.29
8
0
2
4
6
G9afl/fl
Vav.
G9a−/−
Tota
l C
ells
(x10
3)
**
CD90.2 CD127
6
ILC2s control lung inflammation
30th November 2015ASI 2015
Intranasal10μgpapainorcontrol
G9afl/fl
orVav.G9a-/-
BALcounts
BALdifferen als
7
G9a regulates ILC2-dependent lung
inflammation
30th November 2015ASI 2015
8
G9a limits ILC3 program in ILC2s
30th November 2015ASI 2015
9
G9a-dependent H3K9me2 limits ILC3s
30th November 2015ASI 2015
PP
LPL
CD
90
.2
RORγt
10.1
6.4
33.5
18.5
G9afl/fl Vav.G9a− /−
10
G9a-dependent H3K9me2 limits IL-17 in TH2 cells
30th November 2015ASI 2015
Lehnertz et al. (2010) J. Exp. Med. 207: 915.
11
A global role for G9a in type 2 immune responses?
30th November 2015ASI 2015
Licona-Limónetal.Nat.Immunol.14,536(2013)
G9a
G9a
12
Acknowledgements
30th November 2015ASI 2015
Frann Antignano
Menno Oudhoff
Sebastian Scheer
Kyle Burrows
Alistair Chenery
Fabio Rossi
Bernhard Lehnertz
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