Therapeutic application of human leukocyte antigen-G1 improves atopic dermatitis-like skin lesions in mice

Int Immunopharmacol. 2017 Sep:50:202-207. doi: 10.1016/j.intimp.2017.06.026. Epub 2017 Jul 1.

Abstract

Human leukocyte antigen (HLA)-G is an immune checkpoint molecule that plays critical roles in immune response and in triggering inhibitory signaling to immune cells such as T cells, natural killer cells, and antigen-presenting cells. Thus, the application of HLA-G can be considered for treating immune response-related inflammatory disorders. We have previously reported that treatment with HLA-G1 and HLA-G2 ameliorates the joint swelling associated with collagen-induced arthritis of DBA/1 mice, an animal model for rheumatoid arthritis. In this study, we further investigated the effects of HLA-G1 on atopic dermatitis (AD), the most common inflammatory skin disorder. AD-like lesions were induced with the extract of the house dust mite Dermatophagoides farinae in NC/Nga mice. Continuous administration of HLA-G1 ameliorated the AD-like skin lesions in the mice. Furthermore, production of immunoglobulin E, interleukin (IL)-13, and IL-17A was significantly reduced in HLA-G1-treated mice, suggesting a Th2/Th17-mediated immune-inhibitory function of HLA-G1 in vivo. Our studies shed light on novel therapeutic strategies with recombinant HLA-G proteins for immune reaction-mediated chronic inflammatory disorders.

Keywords: Atopic dermatitis; Dermatophagoides farinae; HLA-G1; NC/Nga mice.

MeSH terms

  • Animals
  • Antigens, Dermatophagoides / immunology
  • Dermatitis, Atopic / immunology
  • Dermatitis, Atopic / therapy*
  • Dermatophagoides farinae / immunology
  • Disease Models, Animal
  • Female
  • HLA-G Antigens / therapeutic use*
  • Humans
  • Immunoglobulin E / blood
  • Immunotherapy / methods*
  • Interleukin-13 / metabolism
  • Interleukin-17 / metabolism
  • Mice
  • Mice, Inbred DBA
  • Protein Isoforms
  • Skin / immunology*
  • Skin / pathology
  • Th2 Cells / immunology*

Substances

  • Antigens, Dermatophagoides
  • HLA-G Antigens
  • Interleukin-13
  • Interleukin-17
  • Protein Isoforms
  • Immunoglobulin E