Details

Autor(en) / Beteiligte

• Düster, Mathis
• Becker, Martina
• Gnirck, Ann‐Christin
• Wunderlich, Malte
• Panzer, Ulf
• Turner, Jan‐Eric

Titel

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

Ist Teil von

• European journal of immunology, 2018-08, Vol.48 (8), p.1364-1375

Ort / Verlag

Germany: Wiley Subscription Services, Inc

Erscheinungsjahr

2018

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• 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. Type 2 Innate lymphoid cell (ILC2) abundance in tissues is negatively regulated by T cell‐derived IFN‐γ and myeloid cells‐derived IL‐27 in chronic autoimmune inflammation. In a murine model of systemic lupus erythematosus, ILC2 numbers can be restored by IL‐33 therapy which ameliorates lupus nephritis and prolongs animal survival.