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Isolation and Th17 Differentiation of Naïve CD4 T Lymphocytes
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Isolation and Th17 Differentiation of Naïve CD4 T Lymphocytes

Published on: September 26, 2013

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CMTM4 is a subunit of the IL-17 receptor and mediates autoimmune pathology

Daniela Knizkova1,2, Michaela Pribikova1, Helena Draberova1

  • 1Laboratory of Immunity & Cell Communication, BIOCEV, First Faculty of Medicine, Charles University, Vestec, Czech Republic.

Nature Immunology
|October 21, 2022
PubMed

Insights

The tetra-transmembrane protein CMTM4 is identified as a crucial subunit of the Interleukin-17 receptor (IL-17R), essential for its function. CMTM4 deficiency prevents IL-17A signaling, impacting immune responses and autoimmune disease models.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Interleukin-17A (IL-17A) is vital for immunity against fungal and bacterial infections.
  • IL-17A also contributes to autoimmune diseases like psoriasis and psoriatic arthritis.
  • The precise molecular mechanisms of IL-17 receptor (IL-17R) function are under investigation.

Purpose of the Study:

  • To identify novel components of the IL-17 receptor complex.
  • To elucidate the role of CMTM4 in IL-17R assembly and signaling.
  • To explore CMTM4 as a potential therapeutic target for IL-17-mediated diseases.

Main Methods:

  • Co-immunoprecipitation assays to study protein interactions.
  • Cellular assays using CMTM4-deficient mouse and human cell lines.
  • In vivo studies using CMTM4-deficient mice and experimental models of autoimmune diseases.

Main Results:

  • CMTM4 was identified as a stable subunit of the IL-17 receptor complex, associated with IL-17R subunit C.
  • CMTM4 is critical for IL-17R stability, glycosylation, and plasma membrane localization.
  • CMTM4-deficient cells and mice showed impaired IL-17A signaling and immune cell recruitment.
  • CMTM4-deficient mice exhibited resistance to experimental psoriasis but not experimental autoimmune encephalomyelitis.

Conclusions:

  • CMTM4 is an essential component of the IL-17 receptor, mediating IL-17A signaling.
  • CMTM4 plays a critical role in immune responses and the pathogenesis of specific autoimmune conditions.
  • CMTM4 represents a potential therapeutic target for managing IL-17-driven autoimmune diseases.

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