Cutting edge: the SLAM family receptor Ly108 controls T cell and neutrophil functions

Duncan Howie1, F Stephen Laroux, Massimo Morra

  • 1Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. duncan.howie@path.ox.ac.uk

Insights

Ly108 regulates both adaptive and innate immunity. Mice lacking Ly108 show reduced IL-4 in CD4(+) T cells and defective neutrophil function, increasing susceptibility to bacterial infection.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Ly108 is a cell surface receptor in the Signaling Lymphocytic Activation Molecule family.
  • It is expressed on T cells, B cells, NK cells, and APCs.
  • Ly108 is known to influence NK cell cytotoxicity and T cell cytokine production.

Purpose of the Study:

  • To investigate the role of Ly108 in immune responses.
  • To characterize the immune phenotype of mice with a targeted disruption of Ly108 exons 2 and 3 (Ly108(DeltaE2+3)).

Main Methods:

  • In vitro and in vivo assays were used to assess immune cell function.
  • Analysis included cytokine production (IL-4, IL-6, IL-12, TNF-alpha) and reactive oxygen species (ROS) production in neutrophils.
  • Mice were infected with Leishmania mexicana and Salmonella typhimurium to evaluate susceptibility.

Main Results:

  • Ly108(DeltaE2+3) CD4(+) T cells produced significantly less IL-4 compared to wild-type cells.
  • Ly108(DeltaE2+3) mice were highly susceptible to Salmonella typhimurium infection.
  • Neutrophils from Ly108(DeltaE2+3) mice exhibited defective bactericidal activity due to reduced ROS production, despite increased IL-6, IL-12, and TNF-alpha production.

Conclusions:

  • Ly108 plays a critical role in regulating adaptive immune responses, specifically IL-4 production by CD4(+) T cells.
  • Ly108 is also a key regulator of innate immunity, controlling neutrophil bactericidal function.
  • Ly108 acts as a crucial regulator of both innate and adaptive immunity.

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