Proteomics

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Itch attenuates CD4 T cell proliferation in mice by limiting WBP2 protein stability


ABSTRACT: To mount an anti-pathogen 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 -catenin co-activator 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.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Spleen, T Cell, Lymph Node

SUBMITTER: Hossein Fazelinia  

LAB HEAD: Steven H. Seeholzer

PROVIDER: PXD019272 | Pride | 2021-01-07

REPOSITORIES: Pride

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

Field Natania S NS   Elbulok Omar A OA   Dybas Joseph M JM   Moser Emily K EK   Dar Asif A AA   Spruce Lynn A LA   Fazelinia Hossein H   Seeholzer Steven H SH   Oliver Paula M PM  

European journal of immunology 20200609 10


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 extensive  ...[more]

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