Resolving Discrepancies in Mouse and Human Autoimmunity Studies

By editing primary T cells with CRISPR, researchers begin to settle a long-standing debate about a common autoimmunity risk variant.

Written byNiki Spahich, PhD

| 4 min read

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To understand the inappropriate immune responses that lead to autoimmune disorders, scientists must untangle a complex web of environmental and genetic risk factors. One common autoimmunity risk variant—a mutation that switches an arginine to a tryptophan (R620W) in the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene—associates with numerous autoimmune disorders and nearly doubles a person’s risk of type 1 diabetes, systemic lupus erythematosus, and rheumatoid arthritis.¹ PTPN22 is highly expressed in lymphocytes where it influences T cell receptor (TCR) signaling and T cell activation. While PTPN22 R620W is well known, it is not well understood, leading to opposing opinions about the variant’s consequences.²

When a T cell receptor (TCR) binds its target antigen, a signaling cascade initiates within the cell, driving its proliferation and activation. PTPN22 negatively regulates this response by dephosphorylating key proteins in the pathway.3 The R620W mutation keeps PTPN22 from making it to the membrane where ...

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Meet the Author

Niki Spahich, PhD
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Niki Spahich earned her PhD in genetics and genomics from Duke University, where she studied Haemophilus influenzae membrane proteins that contribute to respiratory infections. She later explored Staphylococcus aureus metabolism during her postdoctoral fellowship in the Department of Microbiology and Immunology at the University of North Carolina at Chapel Hill. Prior to joining The Scientist, Niki taught biology, microbiology, and genetics at various academic institutions. She also developed a passion for science communication in written, visual, and spoken forms, which led her to start Science Riot, a nonprofit dedicated to teaching scientists how to communicate to the public through the lens of comedy. Niki is currently the manager of The Scientist's Creative Services Team.
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