Deficiency of T follicular helper cell Tet3 DNA demethylation inhibits pathogenic IgG2c class switching and chronic GVHD

2.

Socié

G

,

Stone

JV

,

Wingard

JR

, et al.

Long-term survival and late deaths after allogeneic bone marrow transplantation. Late Effects Working Committee of the International Bone Marrow Transplant Registry

.

N Engl J Med

.

1999

;

341

(

1

):

14

-

21

.

3.

Wolff

D

,

Gerbitz

A

,

Ayuk

F

, et al.

Consensus conference on clinical practice in chronic graft-versus-host disease (GVHD): first-line and topical treatment of chronic GVHD

.

Biol Blood Marrow Transplant

.

2010

;

16

(

12

):

1611

-

1628

.

4.

Miklos

D

,

Cutler

CS

,

Arora

M

, et al.

Ibrutinib for chronic graft-versus-host disease after failure of prior therapy

.

Blood

.

2017

;

130

(

21

):

2243

-

2250

.

5.

Jagasia

M

,

Lazaryan

A

,

Bachier

CR

, et al.

ROCK2 inhibition with belumosudil (KD025) for the treatment of chronic graft-versus-host disease

.

J Clin Oncol

.

2021

;

39

(

17

):

1888

-

1898

.

6.

Zeiser

R

,

Polverelli

N

,

Ram

R

, et al.

Ruxolitinib for glucocorticoid-refractory chronic graft-versus-host disease

.

N Engl J Med

.

2021

;

385

(

3

):

228

-

238

.

7.

Wolff

D

,

Cutler

C

,

Lee

SJ

, et al.

Axatilimab in recurrent or refractory chronic graft-versus-host disease

.

N Engl J Med

.

2024

;

391

(

11

):

1002

-

1014

.

8.

Buxbaum

NP

,

Socié

G

,

Hill

GR

, et al.

Chronic GvHD NIH Consensus Project Biology Task Force: evolving path to personalized treatment of chronic GvHD

.

Blood Adv

.

2023

;

7

(

17

):

4886

-

4902

.

9.

Socié

G

,

Kean

LS

,

Zeiser

R

,

Blazar

BR

.

Insights from integrating clinical and preclinical studies advance understanding of graft-versus-host disease

.

J Clin Investig

.

2021

;

131

(

12

):

e149296

.

10.

Baron

F

,

Labopin

M

,

Niederwieser

D

, et al.

Impact of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia: A report from the Acute Leukemia Working Party of the European group for blood and marrow transplantation

.

Leukemia

.

2012

;

26

(

12

):

2462

-

2468

.

11.

Zeiser

R

,

Blazar

BR

.

Pathophysiology of chronic graft-versus-host disease and therapeutic targets

.

N Engl J Med

.

2017

;

377

(

26

):

2565

-

2579

.

12.

Cooke

KR

,

Luznik

L

,

Sarantopoulos

S

, et al.

The biology of chronic graft-versus-host disease: a task force report from the National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease

.

Biol Blood Marrow Transplant

.

2017

;

23

(

2

):

211

-

234

.

13.

Wilhelm

K

,

Ganesan

J

,

Müller

T

, et al.

Graft-versus-host disease is enhanced by extracellular ATP activating P2X7R

.

Nat Med

.

2010

;

16

(

12

):

1434

-

1438

.

14.

Zhao

D

,

Young

JS

,

Chen

Y-H

, et al.

Alloimmune response results in expansion of autoreactive donor CD4 + T cells in transplants that can mediate chronic graft-versus-host disease

.

J Immunol

.

2011

;

186

(

2

):

856

-

868

.

15.

Demasson

A

,

Socié

G

,

Bagot

M

,

Bensussan

A

,

Bouaziz

JD

.

Deficient regulatory B cells in human chronic graft-versus-host disease

.

OncoImmunology

.

2015

;

4

(

7

):

e1016707

.

16.

De Masson

A

,

Bouaziz

JD

,

Le Buanec

H

, et al.

CD24hiCD27+ and plasmablast-like regulatory B cells in human chronic graft-versus-host disease

.

Blood

.

2015

;

125

(

11

):

1830

-

1839

.

17.

Tivol

E

,

Komorowski

R

,

Drobyski

WR

.

Emergent autoimmunity in graft-versus-host disease

.

Blood

.

2005

;

105

(

12

):

4885

-

4891

.

18.

Flynn

R

,

Du

J

,

Veenstra

RG

, et al.

Increased T follicular helper cells and germinal center B cells are required for cGVHD and bronchiolitis obliterans

.

Blood

.

2014

;

123

(

25

):

3988

-

3998

.

19.

Wu

T

,

Young

JS

,

Johnston

H

, et al.

Thymic damage, impaired negative selection, and development of chronic graft-versus-host disease caused by donor CD4 + and CD8 + T cells

.

J Immunol

.

2013

;

191

(

1

):

488

-

499

.

20.

Srinivasan

M

,

Flynn

R

,

Price

A

, et al.

Donor B-cell alloantibody deposition and germinal center formation are required for the development of murine chronic GVHD and bronchiolitis obliterans

.

Blood

.

2012

;

119

(

6

):

1570

-

1580

.

21.

Jin

H

,

Ni

X

,

Deng

R

, et al.

Antibodies from donor B cells perpetuate cutaneous chronic graft-versus-host disease in mice

.

Blood

.

2016

;

127

(

18

):

2249

-

2260

.

22.

Yoo

CB

,

Jones

PA

.

Epigenetic therapy of cancer: past, present and future

.

Nat Rev Drug Discov

.

2006

;

5

(

1

):

37

-

50

.

23.

He

S

,

Xie

F

,

Liu

Y

, et al.

The histone methyltransferase Ezh2 is a crucial epigenetic regulator of allogeneic T-cell responses mediating graft-versus-host disease

.

Blood

.

2013

;

122

(

25

):

4119

-

4128

.

24.

Bashir

Q

,

William

BM

,

Garcia-Manero

G

,

de Lima

M

.

Epigenetic therapy in allogeneic hematopoietic stem cell transplantation

.

Rev Bras Hematol Hemoter

.

2013

;

35

(

2

):

126

-

133

.

25.

Cooper

ML

,

Choi

J

,

Karpova

D

, et al.

Azacitidine mitigates graft-versus-host disease via differential effects on the proliferation of T effectors and natural regulatory T cells in vivo

.

J Immunol

.

2017

;

198

(

9

):

3746

-

3754

.

26.

Ghobadi

A

,

Choi

J

,

Fiala

MA

, et al.

Phase I study of azacitidine following donor lymphocyte infusion for relapsed acute myeloid leukemia post allogeneic stem cell transplantation

.

Leuk Res

.

2016

;

49

:

1

-

6

.

27.

Choi

J

,

Ritchey

J

,

Prior

JL

, et al.

In vivo administration of hypomethylating agents mitigate graft-versus-host disease without sacrificing graft-versus-leukemia

.

Blood

.

2010

;

116

(

1

):

129

-

139

.

28.

Zhao

C

,

Zhang

Y

,

Zheng

H

.

The effects of interferons on allogeneic T cell response in GVHD: the multifaced biology and epigenetic regulations

.

Front Immunol

.

2021

;

12

:

717540

.

29.

Yang

X

,

Lay

F

,

Han

H

,

Jones

PA

. Targeting DNA methylation for epigenetic therapy.

NIH Public Access

;

2010

.

30.

Zhang

D

,

Chen

J

.

Efficacy of decitabine combined with allogeneic hematopoietic stem cell transplantation in the treatment of recurrent and refractory acute myeloid leukemia (AML): a systematic review and meta-analysis

.

Medicine

.

2022

;

101

(

37

):

E30644

.

31.

Kungwankiattichai

S

,

Ponvilawan

B

,

Roy

C

,

Tunsing

P

,

Kuchenbauer

F

,

Owattanapanich

W

.

Maintenance with hypomethylating agents after allogeneic stem cell transplantation in acute myeloid leukemia and myelodysplastic syndrome: a systematic review and meta-analysis

.

Front Med

.

2022

;

9

:

801632

.

32.

Xu

Z

,

Choi

J

,

Cooper

M

, et al.

Phase I-II trial of early azacitidine after matched unrelated donor hematopoietic cell transplantation

.

Transplant Cell Ther

.

2023

;

29

(

11

):

699.e1

-

699.e9

.

33.

Pusic

I

,

Choi

J

,

Fiala

MA

, et al.

Maintenance therapy with decitabine after allogeneic stem cell transplantation for acute myelogenous leukemia and myelodysplastic syndrome

.

Biol Blood Marrow Transplant

.

2015

;

21

(

10

):

1761

-

1769

.

34.

Xuan

L

,

Dai

M

,

Jiang

E

, et al.

The effect of granulocyte-colony stimulating factor, decitabine, and busulfan-cyclophosphamide versus busulfan-cyclophosphamide conditioning on relapse in patients with myelodysplastic syndrome or secondary acute myeloid leukaemia evolving from myelodysplastic syndrome undergoing allogeneic haematopoietic stem-cell transplantation: an open-label, multicentre, randomised, phase 3 trial

.

Lancet Haematol

.

2023

;

10

(

3

):

e178

-

e190

.

35.

Rasmussen

KD

,

Helin

K

.

Role of TET enzymes in DNA methylation, development, and cancer

.

Genes Dev

.

2016

;

30

(

7

):

733

-

750

.

36.

Tsagaratou

A

,

González-Avalos

E

,

Rautio

S

, et al.

TET proteins regulate the lineage specification and TCR-mediated expansion of iNKT cells

.

Nat Immunol

.

2017

;

18

(

1

):

45

-

53

.

37.

Pastor

WA

,

Aravind

L

,

Rao

A

.

TETonic shift: biological roles of TET proteins in DNA demethylation and transcription

.

Nat Rev Mol Cell Biol

.

2013

;

14

(

6

):

341

-

356

.

38.

An

J

,

González-Avalos

E

,

Chawla

A

, et al.

Acute loss of TET function results in aggressive myeloid cancer in mice

.

Nat Commun

.

2015

;

6

(

1

):

10071

.

39.

Tsagaratou

A

,

Rao

A

.

TET proteins and 5-methylcytosine oxidation in the immune system

.

Cold Spring Harb Symp Quant Biol

.

2013

;

78

(

1

):

1

-

10

.

40.

Chua

GNL

,

Wassarman

KL

,

Sun

H

, et al.

Cytosine-based TET enzyme inhibitors

.

ACS Med Chem Lett

.

2019

;

10

(

2

):

180

-

185

.

41.

Zhao

Z

,

Chen

L

,

Dawlaty

MM

, et al.

Combined loss of Tet1 and Tet2 promotes B cell, but not myeloid malignancies, in mice

.

Cell Rep

.

2015

;

13

(

8

):

1692

-

1704

.

42.

Yang

C

,

Li

Z

,

Kang

W

,

Tian

Y

,

Yan

Y

,

Chen

W

.

TET1 and TET3 are essential in induction of Th2-type immunity partly through regulation of IL-4/13A expression in zebrafish model

.

Gene

.

2016

;

591

(

1

):

201

-

208

.

43.

Yue

X

,

Lio

C-WJWJ

,

Samaniego-Castruita

D

,

Li

X

,

Rao

A

.

Loss of TET2 and TET3 in regulatory T cells unleashes effector function

.

Nat Commun

.

2019

;

10

(

1

):

2011

.

44.

Ichiyama

K

,

Chen

T

,

Wang

X

, et al.

The methylcytosine dioxygenase Tet2 promotes DNA demethylation and activation of cytokine gene expression in T cells

.

Immunity

.

2015

;

42

(

4

):

613

-

626

.

45.

Baessler

A

,

Novis

CL

,

Shen

Z

, et al.

Tet2 coordinates with Foxo1 and Runx1 to balance T follicular helper cell and T helper 1 cell differentiation

.

Sci Adv

.

2022

;

8

(

24

):

eabm4982

.

46.

Rasmussen

KD

,

Jia

G

,

Johansen

JV

, et al.

Loss of TET2 in hematopoietic cells leads to DNA hypermethylation of active enhancers and induction of leukemogenesis

.

Genes Dev

.

2015

;

29

(

9

):

910

-

922

.

47.

Ko

M

,

Bandukwala

HS

,

An

J

, et al.

Ten-eleven-translocation 2 (TET2) negatively regulates homeostasis and differentiation of hematopoietic stem cells in mice

.

Proc Natl Acad Sci U S A

.

2011

;

108

(

35

):

14566

-

14571

.

48.

Moran-Crusio

K

,

Reavie

L

,

Shih

A

, et al.

Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation

.

Cancer Cell

.

2011

;

20

(

1

):

11

-

24

.

49.

Aivalioti

MM

,

Bartholdy

BA

,

Pradhan

K

, et al.

PU.1-dependent enhancer inhibition separates Tet2-deficient hematopoiesis from malignant transformation

.

Blood Cancer Discov

.

2022

;

3

(

5

):

444

-

467

.

50.

Lazarenkov

A

,

Sardina

JL

.

Dissecting TET2 regulatory networks in blood differentiation and cancer

.

Cancers

.

2022

;

14

(

3

):

830

.

51.

Paz

K

,

Flynn

R

,

Du

J

, et al.

Small-molecule BCL6 inhibitor effectively treats mice with nonsclerodermatous chronic graft-versus-host disease

.

Blood

.

2019

;

133

(

1

):

94

-

99

.

52.

Panoskaltsis-Mortari

A

,

Tram

KV

,

Price

AP

,

Wendt

CH

,

Blazar

BR

.

A new murine model for bronchiolitis obliterans post-bone marrow transplant

.

Am J Respir Crit Care Med

.

2007

;

176

(

7

):

713

-

723

.

53.

Berns

KI

,

Bond

EC

,

Manning

FJ

;

Resource Sharing in Biomedical Research

.

The American Type Culture Collection

.

National Academies Press (US)

;

1996

.

54.

Glaab

T

,

Taube

C

,

Braun

A

,

Mitzner

W

.

Invasive and noninvasive methods for studying pulmonary function in mice

.

Respir Res

.

2007

;

8

(

1

):

63

.

55.

Pau

G

,

Fuchs

F

,

Sklyar

O

,

Boutros

M

,

Huber

W

.

EBImage-an R package for image processing with applications to cellular phenotypes

.

Bioinformatics

.

2010

;

26

(

7

):

979

-

981

.

56.

Bankhead

P

,

Loughrey

MB

,

Fernández

JA

, et al.

QuPath: open source software for digital pathology image analysis

.

Sci Rep

.

2017

;

7

(

1

):

16878

.

57.

Blazar

BR

,

Taylor

PA

,

McElmurry

R

, et al.

Engraftment of severe combined immune deficient mice receiving allogeneic bone marrow via in utero or postnatal transfer

.

Blood

.

1998

;

92

(

10

):

3949

-

3959

.

58.

Sage

PT

,

Sharpe

AH

.

In vitro assay to sensitively measure TFR suppressive capacity and TFH stimulation of B cell responses

.

Methods Mol Biol

.

2015

;

1291

:

151

-

160

.

59.

Weiss

JM

,

Chen

W

,

Nyuydzefe

MS

, et al.

ROCK2 signaling is required to induce a subset of T follicular helper cells through opposing effects on STATs in autoimmune settings

.

Sci Signal

.

2016

;

9

(

437

):

ra73

.

60.

Du

J

,

Paz

K

,

Flynn

R

, et al.

Pirfenidone ameliorates murine chronic GVHD through inhibition of macrophage infiltration and TGF-β production

.

Blood

.

2017

;

129

(

18

):

2570

-

2580

.

61.

Forcade

E

,

Paz

K

,

Flynn

R

, et al.

An activated Th17-prone T cell subset involved in chronic graft-versus-host disease sensitive to pharmacological inhibition

.

JCI Insight

.

2017

;

2

(

12

):

e92111

.

62.

Alexander

KA

,

Flynn

R

,

Lineburg

KE

, et al.

CSF-1-dependant donor-derived macrophages mediate chronic graft-versus-host disease

.

J Clin Investig

.

2014

;

124

(

10

):

4266

-

4280

.

63.

Shinde

P

,

Howie

HL

,

Stegmann

TC

, et al.

IgG subclass determines suppression versus enhancement of humoral alloimmunity to Kell RBC antigens in mice

.

Front Immunol

.

2020

;

11

:

1516

.

64.

Qiu

A

,

Miller

A

,

Dei

Zotti F

, et al.

Fcg RIV is required for IgG2c mediated enhancement of RBC alloimmunization

.

Front Immunol

.

2022

;

13

:

972723

.

65.

Zhou

J

,

Gao

H

,

Xie

W

,

Li

Y

.

FcgR-binding affinity of monoclonal murine IgG1s carrying different N-linked Fc oligosaccharides

.

2019

;

520

(

1

):

8

-

13

.

66.

Ravetch

JV

,

Bolland

S

.

IgG Fc receptors

.

Annu Rev Immunol

.

2001

;

19

(

1

):

275

-

290

.

67.

Anderson

CL

,

Shen

L

,

Eicher

DM

,

Wewers

MD

,

Gill

JK

.

Phagocytosis mediated by three distinct Fcγ receptor classes on human leukocytes

.

J Exp Med

.

1990

;

171

(

4

):

1333

-

1345

.

68.

Young

JD

,

Ko

SS

,

Cohn

ZA

.

The increase in intracellular free calcium associated with IgGγ2b/γ1 Fc receptor-ligand interactions: role in phagocytosis

.

Proc Natl Acad Sci U S A

.

1984

;

81

(

17

):

5430

-

5434

.

69.

Titus

JA

,

Perez

P

,

Kaubisch

A

,

Garrido

MA

,

Segal

DM

.

Human K/natural killer cells targeted with hetero-cross-linked antibodies specifically lyse tumor cells in vitro and prevent tumor growth in vivo

.

J Immunol

.

1987

;

139

(

9

):

3153

-

3158

.

70.

Ono

M

,

Bolland

S

,

Tempst

P

,

Ravetch

JV

.

Role of the inositol phosphatase SHIP in negative regulation of the immune system by the receptor FcγRIIB

.

Nature

.

1996

;

383

(

6597

):

263

-

266

.

71.

Daëron

M

,

Latour

S

,

Malbec

O

, et al.

The same tyrosine-based inhibition motif, in the intra-cytoplasmic domain of FcγRIIB, regulates negatively BCR-TCR-and FcR-dependent cell activation

.

Immunity

.

1995

;

3

(

5

):

635

-

646

.

72.

Malbec

O

,

Fong

DC

,

Turner

M

, et al.

Fc epsilon receptor I-associated lyn-dependent phosphorylation of Fc gamma receptor IIB during negative regulation of mast cell activation

.

J Immunol

.

1998

;

160

(

4

):

1647

-

1658

.

73.

Rispens

T

,

Huijbers

MG

.

The unique properties of IgG4 and its roles in health and disease

.

Nat Rev Immunol

.

2023

;

23

(

11

):

763

-

778

. 23:11.

74.

Huijbers

MG

,

Querol

LA

,

Niks

EH

, et al.

The expanding field of IgG4-mediated neurological autoimmune disorders

.

Eur J Neurol

.

2015

;

22

(

8

):

1151

-

1161

.

75.

Park

JS

,

Choi

HJ

,

Jung

KM

, et al.

Production of recombinant human IgG1 Fc with beneficial N-glycosylation pattern for anti-inflammatory activity using genome-edited chickens

.

Commun Biol

.

2023

;

6

(

1

):

589

.

76.

Aloulou

M

,

Ben Mkaddem

S

,

Biarnes-Pelicot

M

, et al.

IgG1 and IVIg induce inhibitory ITAM signaling through FcγRIII controlling inflammatory responses

.

Blood

.

2012

;

119

(

13

):

3084

-

3096

.

77.

Zheng

WP

,

Flavell

RA

.

The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells

.

Cell

.

1997

;

89

(

4

):

587

-

596

.

78.

Zhang

DH

,

Cohn

L

,

Ray

P

,

Bottomly

K

,

Ray

A

.

Transcription factor GATA-3 is differentially expressed in murine Th1 and Th2 cells and controls Th2-specific expression of the interleukin-5 gene

.

J Biol Chem

.

1997

;

272

(

34

):

21597

-

21603

.

79.

Luo

W

,

Hu

J

,

Xu

W

,

Dong

J

.

Distinct spatial and temporal roles for Th1, Th2, and Th17 cells in asthma

.

Front Immunol

.

2022

;

13

:

974066

.

80.

Lexberg

MH

,

Taubner

A

,

Förster

A

, et al.

Th memory for interleukin-17 expression is stable in vivo

.

Eur J Immunol

.

2008

;

38

(

10

):

2654

-

2664

.

81.

Harbour

SN

,

Maynard

CL

,

Zindl

CL

,

Schoeb

TR

,

Weaver

CT

.

Th17 cells give rise to Th1 cells that are required for the pathogenesis of colitis

.

Proc Natl Acad Sci U S A

.

2015

;

112

(

22

):

7061

-

7066

.

82.

Hirota

K

,

Duarte

JH

,

Veldhoen

M

, et al.

Fate mapping of IL-17-producing T cells in inflammatory responses

.

Nat Immunol

.

2011

;

12

(

3

):

255

-

263

.

83.

Bending

D

,

De La Peña

H

,

Veldhoen

M

, et al.

Highly purified Th17 cells from BDC2.5NOD mice convert into Th1-like cells in NOD/SCID recipient mice

.

J Clin Investig

.

2009

;

119

(

3

):

565

-

572

.

84.

Lee

YK

,

Turner

H

,

Maynard

CL

, et al.

Late developmental plasticity in the T helper 17 lineage

.

Immunity

.

2009

;

30

(

1

):

92

-

107

.

85.

Chen

T

,

Ali Al-Radhawi

M

,

Sontag

ED

.

A mathematical model exhibiting the effect of DNA methylation on the stability boundary in cell-fate networks

.

Epigenetics

.

2021

;

16

(

4

):

436

-

457

.

86.

Koh

KP

,

Rao

A

.

DNA methylation and methylcytosine oxidation in cell fate decisions

.

Curr Opin Cell Biol

.

2013

;

25

(

2

):

152

-

161

.

87.

Clark

SJ

,

Argelaguet

R

,

Lohoff

T

, et al.

Single-cell multi-omics profiling links dynamic DNA methylation to cell fate decisions during mouse early organogenesis

.

Genome Biol

.

2022

;

23

(

1

):

202

.

88.

Thangavelu

G

,

Zaiken

MC

,

Mohamed

FA

, et al.

Targeting the retinoid X receptor pathway prevents and ameliorates murine chronic graft-versus-host disease

.

Front Immunol

.

2022

;

13

:

765319

.

89.

Chi

X

,

Jin

W

,

Zhao

X

, et al.

RORγt expression in mature TH17 cells safeguards their lineage specification by inhibiting conversion to TH2 cells

.

Sci Adv

.

2022

;

8

(

34

):

eabn7774

.

90.

Salminen

A

,

Kaarniranta

K

,

Hiltunen

M

,

Kauppinen

A

.

Krebs cycle dysfunction shapes epigenetic landscape of chromatin: novel insights into mitochondrial regulation of aging process

.

Cell Signal

.

2014

;

26

(

7

):

1598

-

1603

.

91.

Kaplánek

R

,

Kejík

Z

,

Hajduch

J

, et al.

TET protein inhibitors: potential and limitations

.

Biomed Pharmacother

.

2023

;

166

:

115324

.

92.

Palei

S

,

Weisner

J

,

Vogt

M

, et al.

A high-throughput effector screen identifies a novel small molecule scaffold for inhibition of ten-eleven translocation dioxygenase 2 [published correction appears in RSC Med Chem. 2024;15(2):753-754]

.

RSC Med Chem

.

2022

;

13

(

12

):

1540

-

1548

.

93.

Singh

AK

,

Zhao

B

,

Liu

X

, et al.

Selective targeting of TET catalytic domain promotes somatic cell reprogramming

.

Proc Natl Acad Sci U S A

.

2020

;

117

(

7

):

3621

-

3626

.

94.

Antonyová

V

,

Tatar

A

,

Brogyányi

T

, et al.

Targeting of the mitochondrial TET1 protein by pyrrolo[3,2-b]pyrrole chelators

.

Int J Mol Sci

.

2022

;

23

(

18

):

10850

.

95.

Mo

F

,

Watanabe

N

,

Omdahl

KI

, et al.

Engineering T cells to suppress acute GVHD and leukemia relapse after allogeneic hematopoietic stem cell transplantation

.

Blood

.

2023

;

141

(

10

):

1194

-

1208

.

96.

Hippen

KL

,

Hefazi

M

,

Larson

JH

,

Blazar

BR

.

Emerging translational strategies and challenges for enhancing regulatory T cell therapy for graft-versus-host disease

.

Front Immunol

.

2022

;

13

:

926550

.

97.

Blazar

BR

,

Hill

GR

,

Murphy

WJ

.

Dissecting the biology of allogeneic HSCT to enhance the GvT effect whilst minimizing GvHD

.

Nat Rev Clin Oncol

.

2020

;

17

(

8

):

475

-

492

.

98.

Yu

Y

,

Wang

D

,

Liu

C

, et al.

Prevention of GVHD while sparing GVL effect by targeting Th1 and Th17 transcription factor T-bet and RORγt in mice

.

Blood

.

2011

;

118

(

18

):

5011

-

5020

.