Diet-induced obesity aggravates NK cell-mediated contact hypersensitivity reaction in Rag1-/- mice

Contact Dermatitis. 2021 Sep;85(3):307-316. doi: 10.1111/cod.13871. Epub 2021 May 11.

Abstract

Background: Previous studies showed that natural killer (NK) cells mediate contact hypersensitivity (CHS) reaction. Many reports are showing that obesity promotes several inflammatory diseases. It was shown that diet-induced obesity (DIO) aggravates classical T cell-mediated CHS in mice.

Objectives: To determine whether the high-fat diet (HFD)-induced obesity modulates antigen-specific NK cell-mediated response.

Methods: We evaluated the effect of DIO on NK cell-mediated CHS reaction using a model of dinitrofluorobenzene (DNFB)-induced CHS in Rag1-/- mice.

Results: Rag1-/- mice fed HFD for 8 but not for 4 weeks developed aggravated CHS reaction determined by ear swelling measurement when compared to animals kept on normal diet (ND) prior to DNFB sensitization. The obese Rag1-/- mice presented the adipose tissue inflammation. Furthermore, in vitro analysis showed that feeding with HFD significantly increases interferon γ (IFN-γ) and interleukin (IL)-12p70 and decreases adiponectin concentration in liver mononuclear cell (LMNC) culture supernatants. The flow cytometry analysis of LMNC revealed that HFD treatment prior to DNFB sensitization increases the percentage of NK1.1+ IFN-γ+ cell population and affects the development and maturation of NK1.1+ cells.

Conclusions: In summary, current results suggest that the DIO significantly modulates the local and systemic inflammatory response, contributing to exacerbation of the CHS response mediated by liver NK cells.

Keywords: contact hypersensitivity; liver; natural killer cell; obesity.

MeSH terms

  • Adiponectin / metabolism
  • Animals
  • Cells, Cultured
  • Dermatitis, Allergic Contact / complications
  • Dermatitis, Allergic Contact / immunology*
  • Diet, High-Fat / adverse effects*
  • Disease Models, Animal
  • Flow Cytometry
  • Interferon-gamma / metabolism
  • Interleukin-12 / metabolism
  • Killer Cells, Natural / immunology*
  • Leukocytes, Mononuclear / metabolism
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Obesity / complications
  • Obesity / immunology*
  • Recombinant Proteins / metabolism

Substances

  • Adiponectin
  • Recombinant Proteins
  • interferon gamma-4A
  • Interleukin-12
  • Interferon-gamma