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World J Diabetes. Jul 15, 2017; 8(7): 330-336
Published online Jul 15, 2017. doi: 10.4239/wjd.v8.i7.330
PTPN22 and islet-specific autoimmunity: What have the mouse models taught us?
Giuseppe Galvani, Georgia Fousteri
Giuseppe Galvani, Georgia Fousteri, Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy
Author contributions: Galvani G conducted the literature search, drafted, edited, and approved the final version of the paper; Fousteri G conceived the manuscript, helped with the writing, revised critically, and approved the final version of the manuscript.
Conflict-of-interest statement: The authors declare no conflict-of-interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Georgia Fousteri, MSc, PhD, Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, via Olgettina 60, 20132 Milan, Italy. fousteri.georgia@hsr.it
Telephone: +39-02-26433184 Fax: +39-02-26437759
Received: December 18, 2016
Peer-review started: December 22, 2016
First decision: March 28, 2017
Revised: April 11, 2017
Accepted: May 12, 2017
Article in press: May 15, 2017
Published online: July 15, 2017
Processing time: 197 Days and 2.1 Hours
Abstract

An allelic variant of the protein tyrosin phosphatase non-receptor 22 (PTPN22) gene, PTPN22 R620W, constitutes the strongest non-HLA genetic risk factor for the development of type 1 diabetes (T1D). A number of studies using mouse models have addressed how PTPN22 predisposes to T1D. PTPN22 downmodulation, overexpression or expression of the variant gene in genetically manipulated mice has generated controversial results. These discrepancies probably derive from the fact that PTPN22 has differential effects on innate and adaptive immune responses. Moreover, the effects of PTPN22 are dependent on other genetic variables. Here we discuss these findings and try to explain the discrepancies. Exploring the mechanism by which PTPN22 contributes to islet-specific autoimmunity could help us understand its role in T1D pathogenesis and exploit it as a potential therapeutic target to prevent the disease.

Keywords: Protein tyrosin phosphatase non-receptor 22; Type 1 diabetes; Genetic susceptibility; Mouse model; Autoimmunity; Islet-specific autoimmunity

Core tip: Protein tyrosin phosphatase non-receptor 22 (PTPN22) is the strongest non-HLA gene associated with type 1 diabetes (T1D) and many other autoimmune diseases. Several studies using mouse models have generated controversial results on how PTPN22 predisposes to T1D. In our manuscript we summarize these results and try to explain the discrepancies. Our analysis reveals that PTPN22 assumes different roles in innate and adaptive immunity and its effect is strongly dependent on other genetic variables. Hence, additional studies are required to better understand the mechanism by which PTPN22 predisposes to T1D and to exploit it as a potential therapeutic target in T1D and other autoimmune diseases.