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Publication : Itch attenuates CD4 T-cell proliferation in mice by limiting WBP2 protein stability.

First Author  Field NS Year  2020
Journal  Eur J Immunol Volume  50
Issue  10 Pages  1468-1483
PubMed ID  32459862 Mgi Jnum  J:296428
Mgi Id  MGI:6467206 Doi  10.1002/eji.201948323
Citation  Field NS, et al. (2020) Itch attenuates CD4 T-cell proliferation in mice by limiting WBP2 protein stability. Eur J Immunol 50(10):1468-1483
abstractText  To mount an antipathogen response, CD4 T cells must undergo rapid cell proliferation; however, poorly controlled expansion can result in diseases such as autoimmunity. One important regulator of T-cell activity is the E3 ubiquitin ligase Itch. Itch deficient patients suffer from extensive autoinflammation. Similarly, Itch deficient mice exhibit inflammation characterized by high numbers of activated CD4 T cells. While the role of Itch in limiting CD4 T-cell cytokine production has been extensively studied, it is less clear whether and how Itch regulates proliferation of these cells. We determined that Itch deficient CD4 T cells are hyperproliferative in vitro and in vivo, due to increased S phase entry. Whole cell proteomics analysis of Itch deficient primary mouse CD4 T cells revealed increased abundance of the beta-catenin coactivator WW domain-binding protein 2 (WBP2). Furthermore, Itch deficient cells demonstrate increased WBP2 protein stability, and Itch and WBP2 interact in CD4 T cells. Knockdown of WBP2 in CD4 T cells caused reduced proliferation. Together, our data support that Itch attenuates CD4 T cell proliferation by promoting WBP2 degradation. This study identifies novel roles for Itch and WBP2 in regulating CD4 T cell proliferation, providing insight into how Itch may prevent inflammation.
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