T cell-derived IFN-γ downregulates protective group 2 innate lymphoid cells in murine lupus erythematosus

Eur J Immunol. 2018 Aug;48(8):1364-1375. doi: 10.1002/eji.201747303. Epub 2018 May 17.


Innate lymphoid cells (ILCs) are important regulators of the immune response and play a crucial role in the restoration of tissue homeostasis after injury. GATA-3+ IL-13- and IL-5-producing group 2 innate lymphoid cells (ILC2s) have been shown to promote tissue repair in barrier organs, but despite extensive research on ILCs in the recent years, their potential role in autoimmune diseases is still incompletely understood. In the present study, we investigate the role of ILC2s in the MRL/MpJ-Faslpr (MRL-lpr) mouse model for severe organ manifestation of systemic lupus erythematosus (SLE). We show that in these MRL-lpr mice, progression of lupus nephritis is accompanied with a reduction of ILC2 abundance in the inflamed renal tissue. Proliferation/survival and cytokine production of kidney-residing ILC2s was suppressed by IFN-γ and, to a lesser extent, by IL-27 which were produced by activated T cells and myeloid cells in the nephritic kidney, respectively. Most importantly, restoration of ILC2 numbers by IL-33-mediated expansion ameliorated lupus nephritis and prevented mortality in MRL-lpr mice. In summary, we show here that development of SLE-like kidney inflammation leads to a downregulation of the renal ILC2 response and identify an ILC2-expanding therapy as a promising treatment approach for autoimmune diseases.

Keywords: Autoimmunity; Cytokines; Innate lymphoid cells; MRL-lpr model; Systemic lupus erythematosus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Down-Regulation
  • GATA3 Transcription Factor / metabolism
  • Interferon-gamma / metabolism*
  • Interleukin-13 / metabolism
  • Interleukin-33 / metabolism*
  • Interleukin-5 / metabolism
  • Interleukins / metabolism*
  • Kidney / metabolism
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Erythematosus, Systemic / pathology*
  • Lupus Nephritis / immunology
  • Lupus Nephritis / pathology*
  • Male
  • Mice
  • Mice, Inbred MRL lpr
  • T-Lymphocytes / immunology*


  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • IFNG protein, mouse
  • Il27 protein, mouse
  • Il33 protein, mouse
  • Interleukin-13
  • Interleukin-33
  • Interleukin-5
  • Interleukins
  • Interferon-gamma