PMID- 31732921
OWN - NLM
STAT- MEDLINE
DCOM- 20210621
LR  - 20220531
IS  - 1559-0100 (Electronic)
IS  - 1355-008X (Linking)
VI  - 67
IP  - 3
DP  - 2020 Mar
TI  - Regulation of B cell homeostasis by Ptpn22 contributes to type 1 diabetes in NOD 
      mice.
PG  - 535-543
LID - 10.1007/s12020-019-02120-7 [doi]
AB  - PURPOSE: A coding variant in PTPN22 (C1858T) is one of the most important genetic 
      risk factors in type 1 diabetes (T1D). The role of the PTPN22 risk allele in B 
      cells is still incompletely understood and has not been investigated directly in 
      T1D. This study aimed to explore the role of PTPN22 in the homeostasis of B cells 
      and its influence in T1D. METHODS: Wild-type (WT) and Ptpn22 inducible knockdown 
      (KD) NOD mice were treated with 200 mug/ml doxycycline at the age of 10 weeks for 
      1-2 months. B cell compositions in the bone marrow, peritoneal cavity and spleen 
      were examined. The pathogenicity of Ptpn22 KD B cells was explored by adoptive 
      cell transfer. RESULTS: Ptpn22 silencing increased the frequency of recirculating 
      mature B cells in the bone marrow, decreased the frequency of B-1a cells in the 
      peritoneal cavity and suppressed the formation of marginal zone B cells and 
      plasma cells in the spleen. Changes in the composition of the peripheral B cell 
      compartment caused by altered cell proliferation while rates of apoptosis were 
      not affected. Significantly, co-transfer of Ptpn22 KD B cells with NY8.3 
      diabetogenic T cells diminished the frequency of diabetes in recipient NOD.scid 
      mice compared with co-transfer of WT B cells. CONCLUSIONS: Our study constitutes 
      the first functional study of Ptpn22 in B cells in NOD mice. Our findings suggest 
      that Ptpn22 variation contributes to T1D by modifying the B cell compartment and 
      support a gain-of-function for the PTPN22 disease variant.
FAU - Shi, Xiajie
AU  - Shi X
AD  - Department of Metabolism & Endocrinology, The Second Xiangya Hospital, Key 
      Laboratory of Diabetes Immunology, Central South University, Ministry of 
      Education, National Clinical Research Center for Metabolic Diseases, Changsha, 
      Hunan, 410011, China.
FAU - Shao, Feng
AU  - Shao F
AD  - Department of Metabolism & Endocrinology, The Second Xiangya Hospital, Key 
      Laboratory of Diabetes Immunology, Central South University, Ministry of 
      Education, National Clinical Research Center for Metabolic Diseases, Changsha, 
      Hunan, 410011, China.
FAU - Li, Zhixia
AU  - Li Z
AD  - Department of Metabolism & Endocrinology, The Second Xiangya Hospital, Key 
      Laboratory of Diabetes Immunology, Central South University, Ministry of 
      Education, National Clinical Research Center for Metabolic Diseases, Changsha, 
      Hunan, 410011, China.
FAU - Kang, Lin
AU  - Kang L
AD  - Department of Endocrinology, Shenzhen People's Hospital, The Second Clinical 
      Medical College of Jinan University, The First Affiliated Hospital of Southern 
      University of Science and Technology, Shenzhen, 518020, China.
FAU - Liu, Junbin
AU  - Liu J
AD  - Department of Metabolism & Endocrinology, The Second Xiangya Hospital, Key 
      Laboratory of Diabetes Immunology, Central South University, Ministry of 
      Education, National Clinical Research Center for Metabolic Diseases, Changsha, 
      Hunan, 410011, China.
FAU - Kissler, Stephan
AU  - Kissler S
AD  - Section for Immunobiology, Joslin Diabetes Center, Harvard Medical School, 
      Boston, MA, USA.
FAU - Zhou, Zhiguang
AU  - Zhou Z
AD  - Department of Metabolism & Endocrinology, The Second Xiangya Hospital, Key 
      Laboratory of Diabetes Immunology, Central South University, Ministry of 
      Education, National Clinical Research Center for Metabolic Diseases, Changsha, 
      Hunan, 410011, China. zhouzhiguang@csu.edu.cn.
FAU - Jia, Lijing
AU  - Jia L
AD  - Department of Endocrinology, Shenzhen People's Hospital, The Second Clinical 
      Medical College of Jinan University, The First Affiliated Hospital of Southern 
      University of Science and Technology, Shenzhen, 518020, China. 
      jialijing2012@126.com.
FAU - Zheng, Peilin
AU  - Zheng P
AUID- ORCID: 0000-0002-4712-4903
AD  - Department of Metabolism & Endocrinology, The Second Xiangya Hospital, Key 
      Laboratory of Diabetes Immunology, Central South University, Ministry of 
      Education, National Clinical Research Center for Metabolic Diseases, Changsha, 
      Hunan, 410011, China. plzheng83@163.com.
AD  - Department of Endocrinology, Shenzhen People's Hospital, The Second Clinical 
      Medical College of Jinan University, The First Affiliated Hospital of Southern 
      University of Science and Technology, Shenzhen, 518020, China. plzheng83@163.com.
LA  - eng
GR  - 81670716, 81500600/National Natural Science Foundation of China/International
GR  - 2019JJ30036/Natural Science Foundation of Hunan Province/International
GR  - 2018zzts921/Central South University/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191115
PL  - United States
TA  - Endocrine
JT  - Endocrine
JID - 9434444
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 22)
RN  - EC 3.1.3.48 (Ptpn22 protein, mouse)
SB  - IM
MH  - Alleles
MH  - Animals
MH  - *B-Lymphocytes
MH  - *Diabetes Mellitus, Type 1/genetics
MH  - Homeostasis
MH  - Mice
MH  - Mice, Inbred NOD
MH  - *Protein Tyrosine Phosphatase, Non-Receptor Type 22/genetics
OTO - NOTNLM
OT  - Autoimmunity
OT  - B cells
OT  - PTPN22
OT  - Type 1 diabetes
EDAT- 2019/11/17 06:00
MHDA- 2021/06/22 06:00
CRDT- 2019/11/17 06:00
PHST- 2019/07/14 00:00 [received]
PHST- 2019/10/16 00:00 [accepted]
PHST- 2019/11/17 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2019/11/17 06:00 [entrez]
AID - 10.1007/s12020-019-02120-7 [pii]
AID - 10.1007/s12020-019-02120-7 [doi]
PST - ppublish
SO  - Endocrine. 2020 Mar;67(3):535-543. doi: 10.1007/s12020-019-02120-7. Epub 2019 Nov 
      15.