Janus kinases 1 and 2 regulate chemokine-mediated integrin activation and naïve T-cell homing

Gema Pérez-Rivero1, Graciela Cascio, Silvia Fernández Soriano

  • 1Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Campus de Cantoblanco, Madrid, Spain.

Insights

Janus kinases (JAKs) are crucial for T-cell homing to lymph nodes. Silencing JAK1 and JAK2 impairs chemokine-driven T-cell migration and integrin activation, offering targets for controlling inflammation.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Janus kinases (JAKs) are key in cytokine signaling and their role in chemokine receptor signaling is debated.
  • Understanding JAK involvement in T-cell migration is crucial for immunology and inflammation research.

Purpose of the Study:

  • To investigate the role of JAK1 and JAK2 in T-cell homing to lymph nodes.
  • To elucidate the mechanisms by which JAKs influence chemokine-mediated T-cell migration and integrin activation.

Main Methods:

  • Established a nucleofection model in primary mouse T lymphocytes to silence JAK expression.
  • Assessed T-cell migration, lymph node homing, and intranodal motility in JAK-deficient cells.
  • Analyzed chemokine-induced signaling pathways, including ERM dephosphorylation, F-actin polymerization, and integrin activation.

Main Results:

  • Reduced JAK1 and JAK2 expression significantly impaired naïve T-cell migration towards CXCL12 and CCL21.
  • In vivo homing of JAK1/JAK2-deficient T-cells to lymph nodes was decreased.
  • JAK1/JAK2 deficiency altered chemokine-triggered ERM dephosphorylation, F-actin polymerization, and integrin activation, hindering firm adhesion.

Conclusions:

  • JAK1 and JAK2 are essential for chemokine-induced integrin activation in T-cells.
  • These JAKs play a critical role in T-cell homing to lymph nodes.
  • JAK1/JAK2 may represent therapeutic targets for modulating immune cell extravasation and inflammatory responses.

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