IL-33-Mediated Expansion of Type 2 Innate Lymphoid Cells Protects from Progressive Glomerulosclerosis.
Innate lymphoid cells (ILCs) have an important role in the immune system's response to different forms of infectious and noninfectious pathologies. In particular, IL-5- and IL-13-producing type 2 ILCs (ILC2s) have been implicated in repair mechanisms that restore tissue integrity after injury. However, the presence of renal ILCs in humans has not been reported. In this study, we show that ILC populations are present in the healthy human kidney. A detailed characterization of kidney-residing ILC populations revealed that IL-33 receptor-positive ILC2s are a major ILC subtype in the kidney of humans and mice. Short-term IL-33 treatment in mice led to sustained expansion of IL-33 receptor-positive kidney ILC2s and ameliorated adriamycin-induced glomerulosclerosis. Furthermore, the expansion of ILC2s modulated the inflammatory response in the diseased kidney in favor of an anti-inflammatory milieu with a reduction of pathogenic myeloid cell infiltration and a marked accumulation of eosinophils that was required for tissue protection. In summary, kidney-residing ILC2s can be effectively expanded in the mouse kidney by IL-33 treatment and are central regulators of renal repair mechanisms. The presence of ILC2s in the human kidney tissue identifies these cells as attractive therapeutic targets for CKD in humans.
III. Medical Clinic.
Jan-Hendrik
JH
Riedel
III. Medical Clinic.
Martina
M
Becker
III. Medical Clinic.
Kerstin
K
Kopp
III. Medical Clinic.
Mathis
M
Düster
III. Medical Clinic.
Silke R
SR
Brix
III. Medical Clinic.
Catherine
C
Meyer-Schwesinger
Deparment of Urology, and.
Luis A
LA
Kluth
III. Medical Clinic.
Ann-Christin
AC
Gnirck
III. Medical Clinic.
Madena
M
Attar
III. Medical Clinic.
Sonja
S
Krohn
Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Boris
B
Fehse
III. Medical Clinic.
Rolf A K
RAK
Stahl
III. Medical Clinic.
Ulf
U
Panzer
III. Medical Clinic, j.turner@uke.de.
Jan-Eric
JE
Turner
D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D018450:Disease Progression; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D000067596:Interleukin-33 / Q000502:physiology* / Q000627:therapeutic use; D007674:Kidney Diseases / Q000276:immunology* / Q000517:prevention & control; D007678:Kidney Glomerulus / Q000473:pathology*; D008214:Lymphocytes / Q000145:classification / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012598:Sclerosis / Q000276:immunology / Q000517:prevention & control
D000067596:Interleukin-33
IL-33; glomerulosclerosis; innate lymphoid cells