Transfusion of CD206+ M2 Macrophages Ameliorates Antibody-Mediated Glomerulonephritis in Mice

Du, Qiuna; Tsuboi, Naotake; Shi, Yiqin; Ito, Sachiko; Sugiyama, Yutaka; Furuhashi, Kazuhiro; Endo, Nobuhide; Kim, Hangsoo; Kuriyama, Takayuki; Akiyama, Shin–ichi; Matsuo, Seiichi; Isobe, K; Maruyama, Shoichi

doi:10.1016/j.ajpath.2016.08.012

Cited by 38 publications

(23 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A previous study demonstrated that the amelioration of kidney injury in NTN is accompanied by an increase in the percentage of CD4 þ FoxP3 þ regulatory T cells in the KLN following transfusion of immunoregulatory CD206 þ M2 macrophages. 22 However, our study is the first to focus specifically on the association between the proinflammatory activity of FRCs in the KLN and kidney damage in crescentic GN.…”

Section: Discussionmentioning

confidence: 97%

Activation of fibroblastic reticular cells in kidney lymph node during crescentic glomerulonephritis

Kasinath

Yilmam

Uehara

et al. 2019

Kidney International

View full text Add to dashboard Cite

C rescentic glomerulonephritis (GN) is a rapidly progressive inflammatory condition affecting the kidneys that can lead to renal failure in humans within days. 1,2 If left untreated, the majority of patients with crescentic GN will die or become dialysis-dependent within 6 months. 3 The central role of CD4 þ T cell-mediated renal injury in nephrotoxic serum nephritis (NTN), a classic experimental anti-glomerular basement membrane antibody-mediated model of crescentic GN, has been well established. 4-10 Several previous studies have elucidated the role of fibroblastic reticular cells (FRCs), the prominent cells that comprise the stromal compartment of the lymph node (LN), in the activation of an immune response. 11-18 FRCs express the membrane glycoprotein podoplanin (PDPN), but they do not express the leukocyte marker CD45 or the vascular marker CD31, a unique cellular signature in the LN. 15 FRCs secrete the chemokines CCL19, CCL21, and CXCL12, which promote the trafficking of naïve T cells into the LN through specialized vasculature known as high endothelial venules (HEVs). 14 FRCs also maintain the integrity of HEVs through interactions between PDPN on the FRCs and C-type lectin-like receptor 2 on platelets. 19 The chemokines secreted by FRCs contain the newly arrived T cells within the paracortex (T-cell zone) of the LN, where the FRCs provide conduits on which these naïve T cells and antigen-presenting cells migrate and interact, resulting in activation of the T cells. 14 Though the kidney has been proven to be a site of recruitment for activated CD4 þ T helper 1 (Th1) and Th17 cells via expression of chemokines such as CCL20 and CXCL9, 10 the role of the kidney lymph node (KLN) as a secondary lymphoid organ where these T cells are also activated in NTN has not yet been explored in depth. 20 CD4 þ T cells are activated in the spleen during NTN, 10 but splenectomy does not affect kidney damage significantly in these mice. 21 This finding raises the hypothesis that the KLN may be the key secondary lymphoid organ responsible for propagation of the immune response in NTN. The objectives of this study are to explore the phenotypic changes that occur to FRCs in the KLN during the early stages of the immune response and examine the effects that modulation of the activity of FRCs has on kidney damage in NTN.

show abstract

Section: Discussionmentioning

confidence: 97%

Activation of fibroblastic reticular cells in kidney lymph node during crescentic glomerulonephritis

Kasinath

Yilmam

Uehara

et al. 2019

Kidney International

View full text Add to dashboard Cite

show abstract

“…Thus, augmenting M1 macrophage differentiation renders multiple organs including the kidney more susceptible to damage, whereas transfer of CD206 + M2 macrophages attenuates glomerular injury during NTN. 19 To further investigate the effects of KLF4 on renal macrophage polarization, infiltrating CD11b + Ly6C hi inflammatory macrophages were sorted from kidneys of KLF4 MKO mice and WTs. Among the proinflammatory M1 cytokines, only TNFa in sorted CD11b + Ly6C hi was significantly increased, whereas levels of M2 markers were not altered in KLF4deficient renal macrophages.…”

Section: Augmented Renal Fibrosis and Necroptosis In Klf4 Mko Mice Ismentioning

confidence: 99%

KLF4 in Macrophages Attenuates TNFα-Mediated Kidney Injury and Fibrosis

Wen¹,

Lu²,

Ren³

et al. 2019

JASN

103

View full text Add to dashboard Cite

BackgroundPolarized macrophage populations can orchestrate both inflammation of the kidney and tissue repair during CKD. Proinflammatory M1 macrophages initiate kidney injury, but mechanisms through which persistent M1-dependent kidney damage culminates in fibrosis require elucidation. Krüppel-like factor 4 (KLF4), a zinc-finger transcription factor that suppresses inflammatory signals, is an essential regulator of macrophage polarization in adipose tissues, but the effect of myeloid KLF4 on CKD progression is unknown.MethodsWe used conditional mutant mice lacking KLF4 or TNFα (KLF4’s downstream effector) selectively in myeloid cells to investigate macrophage KLF4’s role in modulating CKD progression in two models of CKD that feature robust macrophage accumulation, nephrotoxic serum nephritis, and unilateral ureteral obstruction.ResultsIn these murine CKD models, KLF4 deficiency in macrophages infiltrating the kidney augmented their M1 polarization and exacerbated glomerular matrix deposition and tubular epithelial damage. During the induced injury in these models, macrophage-specific KLF4 deletion also exacerbated kidney fibrosis, with increased levels of collagen 1 and α-smooth muscle actin in the injured kidney. CD11b+Ly6Chi myeloid cells isolated from injured kidneys expressed higher levels of TNFα mRNA versus wild-type controls. In turn, mice bearing macrophage-specific deletion of TNFα exhibited decreased glomerular and tubular damage and attenuated kidney fibrosis in the models. Moreover, treatment with the TNF receptor-1 inhibitor R-7050 during nephrotoxic serum nephritis reduced damage, fibrosis, and necroptosis in wild-type mice and mice with KLF4-deficient macrophages, and abrogated the differences between the two groups in these parameters.ConclusionsThese data indicate that macrophage KLF4 ameliorates CKD by mitigating TNF-dependent injury and fibrosis.

show abstract

“…The above PRR-targeting agents primarily inhibit inflammation and decrease M1 macrophage polarization. Some agents that directly target macrophages and macrophage polarization, for example, injection of genetically overexpressed IL-4 macrophages [ 91 ] or transfusion of IL-4/IL-13-differentiated bone-marrow macrophages [ 92 ] have shown a consequent M2 macrophage phenotype and reduction of the degree of renal glomerular inflammation and injury in rodents with nephrotoxic nephritis. Curcumin, a glucose metabolic homeostasis modulator, suppresses the M1 response while promoting an M2 response that enhances macrophage-mediated phagocytosis [ 93 ], and could draw attention for potential application in CKD.…”

Section: Introductionmentioning

confidence: 99%

Macrophage polarization in innate immune responses contributing to pathogenesis of chronic kidney disease

et al. 2020

View full text Add to dashboard Cite

Chronic kidney disease (CKD) is characterized by inflammation, injury and fibrosis. Dysregulated innate immune responses mediated by macrophages play critical roles in progressive renal injury. The differentiation and polarization of macrophages into pro-inflammatory ‘M1’ and anti-inflammatory ‘M2’ states represent the two extreme maturation programs of macrophages during tissue injury. However, the effects of macrophage polarization on the pathogenesis of CKD are not fully understood. In this review, we discuss the innate immune mechanisms underlying macrophage polarization and the role of macrophage polarization in the initiation, progression, resolution and recurrence of CKD. Macrophage activation and polarization are initiated through recognition of conserved endogenous and exogenous molecular motifs by pattern recognition receptors, chiefly, Toll-like receptors (TLRs), which are located on the cell surface and in endosomes, and NLR inflammasomes, which are positioned in the cytosol. Recent data suggest that genetic variants of the innate immune molecule apolipoprotein L1 (APOL1) that are associated with increased CKD prevalence in people of African descent, mediate an atypical M1 macrophage polarization. Manipulation of macrophage polarization may offer novel strategies to address dysregulated immunometabolism and may provide a complementary approach along with current podocentric treatment for glomerular diseases.

show abstract

Transfusion of CD206+ M2 Macrophages Ameliorates Antibody-Mediated Glomerulonephritis in Mice

Cited by 38 publications

References 58 publications

Activation of fibroblastic reticular cells in kidney lymph node during crescentic glomerulonephritis

Activation of fibroblastic reticular cells in kidney lymph node during crescentic glomerulonephritis

KLF4 in Macrophages Attenuates TNFα-Mediated Kidney Injury and Fibrosis

Macrophage polarization in innate immune responses contributing to pathogenesis of chronic kidney disease

Contact Info

Product

Resources

About