title: IL-25 induces M2 macrophages and reduces renal injury in proteinuric kidney disease.
abstract: The kidney contains receptors for the cytokine IL-25, but the effects of IL-25 in CKD are unknown. Here, we induced adriamycin nephropathy in both BALB/c mice and severe combined immunodeficient (SCID) mice, and we injected IL-25 for 7 consecutive days starting at day 5 after adriamycin administration. BALB/c mice treated with IL-25 had less glomerulosclerosis, tubular atrophy, interstitial expansion, and proteinuria than control mice at day 28. IL-25 increased the levels of IL-4 and IL-13 in serum, kidney, renal draining lymph nodes, and CD4+ lymphocytes. IL-25 also directly suppressed effector macrophages in vitro and in vivo and induced alternatively activated (M2) macrophages in vivo. However, in SCID mice and in BALB/c mice treated with IL-4/13-neutralizing antibody, IL-25 failed to protect against renal injury and did not induce M2. In conclusion, IL-25 protects against renal injury in adriamycin nephropathy in mice by, at least in part, inducing Th2 immune responses.
authors: Centre for Transplant and Renal Research, Westmead Millennium Institute, The University of Sydney, Sydney, NSW, Australia.
authors: Qi
authors: Q
authors: Cao
authors: Changqi
authors: C
authors: Wang
authors: Dong
authors: D
authors: Zheng
authors: Ya
authors: Y
authors: Wang
authors: Vincent W S
authors: VW
authors: Lee
authors: Yuan Min
authors: YM
authors: Wang
authors: Guoping
authors: G
authors: Zheng
authors: Thian Kui
authors: TK
authors: Tan
authors: Di
authors: D
authors: Yu
authors: Stephen I
authors: SI
authors: Alexander
authors: David C H
authors: DC
authors: Harris
authors: Yiping
authors: Y
authors: Wang
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000517:prevention & control; D000818:Animals; D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D005923:Glomerulosclerosis, Focal Segmental / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D008262:Macrophage Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D011507:Proteinuria / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000187:drug effects*
chemical_list: D000903:Antibiotics, Antineoplastic; D018793:Interleukin-13; D007378:Interleukins; C442281:Mydgf protein, mouse; D015847:Interleukin-4; D004317:Doxorubicin