Regulation of B cell homeostasis by Ptpn22 contributes to type 1 diabetes in NOD mice

Shi, Xiajie1; Shao, Feng1; Li, Zhixia1; Kang, Lin2; Liu, Junbin1; Kissler, Stephan3; Zhou, Zhiguang1; Jia, Lijing2; Zheng, Peilin1,2

2020-03

10.1007/s12020-019-02120-7

ENDOCRINE: INTERNATIONAL JOURNAL OF BASIC AND CLINICAL ENDOCRINOLOGY   影响因子和分区

1355-008X

1559-0100

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 mu g/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.

Type 1 diabetes PTPN22 B cells Autoimmunity

SCI

英语

通讯

Central South University[2018zzts921]

Endocrinology & Metabolism

Endocrinology & Metabolism

WOS:000518803900004

SPRINGER

BIOLOGY & BIOCHEMISTRY

Web of Science

1.Cent South Univ, Xiangya Hosp 2, Natl Clin Res Ctr Metab Dis, Dept Metab & Endocrinol,Minist Educ,Key Lab Diabe, Changsha 410011, Hunan, Peoples R China
2.Southern Univ Sci & Technol, Jinan Univ, Shenzhen Peoples Hosp,Clin Med Coll 2, Dept Endocrinol,Affiliated Hosp 1, Shenzhen 518020, Peoples R China
3.Harvard Med Sch, Joslin Diabet Ctr, Sect Immunobiol, Boston, MA 02115 USA

Shi, Xiajie,Shao, Feng,Li, Zhixia,et al. Regulation of B cell homeostasis by Ptpn22 contributes to type 1 diabetes in NOD mice[J]. ENDOCRINE: INTERNATIONAL JOURNAL OF BASIC AND CLINICAL ENDOCRINOLOGY,2020,67(3):535-543.

Shi, Xiajie.,Shao, Feng.,Li, Zhixia.,Kang, Lin.,Liu, Junbin.,...&Zheng, Peilin.(2020).Regulation of B cell homeostasis by Ptpn22 contributes to type 1 diabetes in NOD mice.ENDOCRINE: INTERNATIONAL JOURNAL OF BASIC AND CLINICAL ENDOCRINOLOGY,67(3),535-543.

Shi, Xiajie,et al."Regulation of B cell homeostasis by Ptpn22 contributes to type 1 diabetes in NOD mice".ENDOCRINE: INTERNATIONAL JOURNAL OF BASIC AND CLINICAL ENDOCRINOLOGY 67.3(2020):535-543.