NK cells require IL-28R for optimal in vivo activity

Area of Science:

• Immunology
• Cellular Biology
• Infectious Disease

Background:

• Natural killer (NK) cells are vital innate immune cells involved in tumor surveillance and inflammation.
• While Type I interferons (IFN-I) are well-studied, the role of Type III interferons (IFN-III) in NK cell regulation remains largely unknown.

Purpose of the Study:

• To investigate the direct role of Type III interferon receptor (IL-28R) signaling in NK cell effector functions.
• To elucidate the impact of IFN-λ on NK cell-mediated immunity in models of infection and cancer.

Main Methods:

• Utilized IL-28R-deficient mice to assess responses to lipopolysaccharide (LPS) and cecal ligation puncture (CLP) induced sepsis.
• Evaluated tumor metastasis and carcinogen-induced tumor formation in IL-28R-deficient mice.
• Investigated NK cell function by transferring IL-28R-deficient NK cells into lymphocyte-deficient recipients.

Main Results:

• IL-28R-deficient mice exhibited altered cytokine profiles and dysregulated responses during sepsis.
• Absence of IL-28R signaling led to increased susceptibility to tumor metastasis and development.
• Loss of IL-28R in NK cells impaired IFN-γ production and enhanced tumor metastasis.

Conclusions:

• Type III interferons (IFN-λ) directly regulate NK cell effector functions in vivo.
• IFN-λ signaling plays a critical role in NK cell-mediated protection against infections and tumor progression.
• IFN-λ acts both independently and in concert with Type I interferons (IFN-I) to modulate NK cell immunity.