title: Discrete functions of M2a and M2c macrophage subsets determine their relative efficacy in treating chronic kidney disease.
abstract: Two types of alternatively activated macrophages, M(2a) induced by IL-4/IL-13 and M(2c) by IL-10/TGF-β, exhibit anti-inflammatory functions in vitro and protect against renal injury in vivo. Since their relative therapeutic efficacy is unclear, we compared the effects of these two macrophage subsets in murine adriamycin nephrosis. Both subsets significantly reduced renal inflammation and renal injury; however, M(2c) macrophages more effectively reduced glomerulosclerosis, tubular atrophy, interstitial expansion, and proteinuria than M(2a) macrophages. The M(2c) macrophages were also more effective than M(2a) in reduction of macrophage and CD4(+) T-cell infiltration in kidney. Moreover, nephrotic mice treated with M(2c) had a greater reduction in renal fibrosis than those treated with M(2a). M(2c) but not M(2a) macrophages induced regulatory T cells (Tregs) from CD4(+)CD25(-) T cells in vitro, and increased Treg numbers in local draining lymph nodes of nephrotic mice. To determine whether the greater protection with M(2c) was due to their capability to induce Tregs, the Tregs were depleted by PC61 antibody in nephrotic mice treated with M(2a) or M(2c). Treg depletion diminished the superior effects of M(2c) compared to M(2a) in protection against renal injury, inflammatory infiltrates, and renal fibrosis. Thus, M(2c) are more potent than M(2a) macrophages in protecting against renal injury due to their ability to induce Tregs.
authors: Emergency Department, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, People's Republic of China.
authors: Junyu
authors: J
authors: Lu
authors: Qi
authors: Q
authors: Cao
authors: Dong
authors: D
authors: Zheng
authors: Yan
authors: Y
authors: Sun
authors: Changqi
authors: C
authors: Wang
authors: Xiao
authors: X
authors: Yu
authors: Ya
authors: Y
authors: Wang
authors: Vincent W S
authors: VW
authors: Lee
authors: Guoping
authors: G
authors: Zheng
authors: Thian K
authors: TK
authors: Tan
authors: Xin
authors: X
authors: Wang
authors: Stephen I
authors: SI
authors: Alexander
authors: David C H
authors: DC
authors: Harris
authors: Yiping
authors: Y
authors: Wang
mesh_terms: D019264:Adoptive Transfer / Q000379:methods*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002478:Cells, Cultured; D019468:Disease Management; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000009:adverse effects; D066298:In Vitro Techniques; D008264:Macrophages / Q000145:classification* / Q000166:cytology / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009401:Nephrosis / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D010641:Phenotype; D051436:Renal Insufficiency, Chronic / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000502:physiology
chemical_list: D004317:Doxorubicin