PTPN22 inhibition resets defective human central B cell tolerance
Jean-Nicolas Schickel
(1)
,
Marcel Kuhny
(1)
,
Alessia Baldo
(1)
,
Jason M Bannock
(1)
,
Christopher Massad
(1)
,
Haowei Wang
(1)
,
Nathan Katz
(1)
,
Tyler Oe
(1)
,
Laurence Menard
(1)
,
Pauline Soulas-Sprauel
(2, 3)
,
Till Strowig
(1)
,
Richard Flavell
(4)
,
Eric Meffre
(1)
Pauline Soulas-Sprauel
- Fonction : Auteur
- PersonId : 1115889
Till Strowig
- Fonction : Auteur
- PersonId : 792413
- ORCID : 0000-0003-0185-1459
Résumé
The 1858T protein tyrosine phosphatase nonreceptor type 22 (PTPN22 T) allele is one of the main risk factors associated with many autoimmune diseases and correlates with a defective removal of developing autoreactive B cells in humans. To determine whether inhibiting PTPN22 favors the elimination of autoreactive B cells, we first demonstrated that the PTPN22 T allele interfered with the establishment of central B cell tolerance using NOD-scid-common γ chain knockout (NSG) mice engrafted with human hematopoietic stem cells expressing this allele. In contrast, the inhibition of either PTPN22 enzymatic activity or its expression by RNA interference restored defective central B cell tolerance in this model. Thus, PTPN22 blockade may represent a therapeutic strategy for the prevention or treatment of autoimmunity.
Domaines
ImmunologieFormat du dépôt | Notice |
---|---|
Type de dépôt | Article dans une revue |
Titre |
en
PTPN22 inhibition resets defective human central B cell tolerance
|
Résumé |
en
The 1858T protein tyrosine phosphatase nonreceptor type 22 (<i>PTPN22 T</i>) allele is one of the main risk factors associated with many autoimmune diseases and correlates with a defective removal of developing autoreactive B cells in humans. To determine whether inhibiting PTPN22 favors the elimination of autoreactive B cells, we first demonstrated that the <i>PTPN22 T</i> allele interfered with the establishment of central B cell tolerance using NOD-scid-common γ chain knockout (NSG) mice engrafted with human hematopoietic stem cells expressing this allele. In contrast, the inhibition of either PTPN22 enzymatic activity or its expression by RNA interference restored defective central B cell tolerance in this model. Thus, PTPN22 blockade may represent a therapeutic strategy for the prevention or treatment of autoimmunity.
|
Auteur(s) |
Jean-Nicolas Schickel
1
, Marcel Kuhny
1
, Alessia Baldo
1
, Jason M Bannock
1
, Christopher Massad
1
, Haowei Wang
1
, Nathan Katz
1
, Tyler Oe
1
, Laurence Menard
1
, Pauline Soulas-Sprauel
2, 3
, Till Strowig
1
, Richard Flavell
4
, Eric Meffre
1
1
Yale University [New Haven]
( 46674 )
- 157 Church Street, New Haven, CT 06510-2100
- États-Unis
2
I2CT -
Immunologie, Immunopathologie et Chimie Thérapeutique
( 1071567 )
- Institut de Biologie Moléculaire et Cellulaire
2 Allée Konrad Roentgen
67084 Strasbourg
- France
3
IBMC -
Institut de biologie moléculaire et cellulaire
( 1956 )
- I.B.M.C. 15 Rue René Descartes 67084 STRASBOURG CEDEX
- France
4
HHMI -
Howard Hughes Medical Institute
( 91969 )
- États-Unis
|
Langue du document |
Anglais
|
Date de production/écriture |
2016
|
Nom de la revue |
|
Vulgarisation |
Non
|
Comité de lecture |
Oui
|
Audience |
Non spécifiée
|
Date de publication |
2016
|
Volume |
1
|
Numéro |
1
|
URL éditeur |
https://europepmc.org/articles/PMC5127630
|
Domaine(s) |
|
DOI | 10.1126/sciimmunol.aaf7153 |
Pubmed Id | 27917411 |
PubMed Central | PMC5127630 |
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