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Related Concept Videos

T Cell Types and Functions01:24

T Cell Types and Functions

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When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
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T Cell Activation and Clonal Selection01:22

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T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
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Common myeloid progenitors (CMPs) are oligopotent cells that can differentiate into granulocytes and macrophages. Granulocytes and macrophages are essential for protecting the body against bacterial, viral, or fungal infections. They migrate from the bone marrow into the circulating blood to reach specific tissue sites where they differentiate and help in immune surveillance. However, they survive only for a few days and must be continuously made available to the organism to maintain a robust...
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Updated: Sep 16, 2025

SorLA and CLC:CLF-1-dependent Downregulation of CNTFRα as Demonstrated by Western Blotting, Inhibition of Lysosomal Enzymes, and Immunocytochemistry
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CLCF1 promotes IL12Rβ2 proteolysis and limits Th1 differentiation.

Véronique Laplante1, Marine Rousseau2, Sarah Pasquin2

  • 1Département de pharmacologie et physiologie, Université de Montréal, Montréal, Québec H3T 1J4, Canada.

Cytokine
|July 8, 2025
PubMed
Summary
This summary is machine-generated.

Cardiotrophin-like cytokine factor 1 (CLCF1) negatively regulates Interleukin-12 (IL12) activity by promoting IL12 receptor degradation. This finding suggests CLCF1 as a therapeutic target for inflammatory Th1 cell responses.

Keywords:
Cardiotrophin-like cytokine factor 1Cytokine-receptor interactionIL12IL12Rβ2ProteolysisTh1 cells

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Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Cardiotrophin-like cytokine factor 1 (CLCF1) is an IL6/IL12 family cytokine involved in immune modulation and motor neuron development.
  • CLCF1's specific roles in immune cell regulation, particularly T cells, require further elucidation.

Purpose of the Study:

  • To investigate the immune-modulating functions of CLCF1, focusing on its interaction with the IL12 signaling pathway.
  • To characterize a novel mouse model lacking CLCF1 in hematopoietic cells.

Main Methods:

  • Utilized a Vav-promoter driven Clcf1 knockout mouse model.
  • Stimulated CD4+ T cells with IL12 and measured Interferon-gamma (IFNγ) production.
  • Assessed IL12 receptor beta 2 (IL12Rβ2) expression levels and degradation pathways.

Main Results:

  • Clcf1-deficient CD4+ T cells exhibited increased IFNγ production upon IL12 stimulation.
  • CLCF1 was found to downregulate IL12Rβ2 expression.
  • CLCF1 directly interacts with IL12Rβ2, promoting its proteasomal degradation independently of ubiquitination.

Conclusions:

  • CLCF1 acts as a negative regulator of IL12 activity, impacting Th1 cell responses.
  • CLCF1's role in mediating protein degradation may represent a novel biological function.
  • CLCF1 presents a potential therapeutic target for modulating inflammatory conditions driven by Th1 cells.