Ly6cLo non-classical monocytes promote resolution of rhesus rotavirus-mediated perinatal hepatic inflammation

Alkhani, Anas; Levy, Claire S.; Tsui, Margaret; Rosenberg, Katherine; Polovina, Katya; Mattis, Aras N.; Mack, Matthias; Dyken, Steven J. Van; Wang, Bruce M.; Maher, Jacquelyn J.; Nijagal, Amar

doi:10.1038/s41598-020-64158-2

Cited by 18 publications

(28 citation statements)

References 51 publications

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“…As we see here, Ly6c, a marker of classically activated monocyte/macrophages [ 33 , 34 ], is also a good marker to identify blood vessels in mice.…”

Section: Discussionmentioning

confidence: 88%

“…Ly6c (lymphocyte antigen 6 complex, locus C1) is a monocyte/macrophage cell differentiation antigen commonly used to differentiate classical monocytes (Ly6c high ) from non-classical ones (Ly6c low ) [ 33 , 34 ]. Alliot et al, in 1998 [ 30 ], showed that Ly6c was expressed in the blood vessels of the mouse brain but not in microglial cells, and we wondered whether the same was true for the healthy and diseased retina.…”

Section: Introductionmentioning

confidence: 99%

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Ly6c as a New Marker of Mouse Blood Vessels: Qualitative and Quantitative Analyses on Intact and Ischemic Retinas

Martínez-Carmona

Lucas‐Ruiz

Gallego‐Ortega

et al. 2021

IJMS

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Ly6c is an antigen commonly used to differentiate between classical and non-classical monocytes/macrophages. Here we show its potential as a marker of the mouse vasculature, particularly of the retinal vascular plexuses. Ly6c was immunodetected in several tissues of C57BL/6 mice using isolectin IB4 as the control of vasculature staining. In the retina, Ly6c expression was analyzed qualitatively and quantitatively in intact, ischemic, and contralateral retinas from 0 to 30 days after the insult. Ly6c expression was observed in all organs and tissues tested, with a brighter signal and more homogeneous staining than the IB4. In the retinas, Ly6c was well expressed, allowing a detailed study of their anatomy. The three retinal plexuses were morphologically different, and from the superficial to the deep one occupied 15 ± 2, 24 ± 7, and 38 ± 1.4 percent of the retinal surface, respectively. In the injured retinas, there was extravasation of the classically activated monocyte/macrophages (Ly6chigh) and the formation of new vessels in the superficial plexus, increasing the area occupied by it to 25 ± 1%. In the contralateral retinas, the superficial plexus area decreased gradually, reaching significance at 30 days, and Ly6c expression progressively disappeared in the intermediate and deep plexuses. Although the role of Ly6c in vascular endothelial cell function is still not completely understood, we demonstrate here that Ly6c can be used as a new specific marker of the mouse vasculature and to assess, qualitatively and quantitatively, vascular changes in health and disease.

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“…As we see here, Ly6c, a marker of classically activated monocyte/macrophages [ 33 , 34 ], is also a good marker to identify blood vessels in mice.…”

Section: Discussionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Ly6c as a New Marker of Mouse Blood Vessels: Qualitative and Quantitative Analyses on Intact and Ischemic Retinas

Martínez-Carmona

Lucas‐Ruiz

Gallego‐Ortega

et al. 2021

IJMS

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“…Individual CMPs and TMPs were distinguished based on the expression of CD34, Fc1R, Flt3, Ly6C, and CD115 ( Figure 1a,b )[12]. Since our previous work demonstrated a limited role for T and B lymphocytes in the pathogenesis of PLI[4], lymphoid progenitors were not quantified in this study. We first quantified the lineage-negative (Lin -ve ) compartment in the liver and found that the percentage and number of Lin -ve cells did not differ significantly between P3 and P14 liver ( Figure 1c ) and the number of specific HSPC populations, including CMPs, and TMPs, were significantly lower at P14 than at P3 ( Figure 1c,d ).…”

Section: Resultsmentioning

confidence: 99%

“…All HSPCs were identified from flow plots as shown in Figure 3a . Mature populations were identified using a previously published gating strategy[4]. PLI significantly increased the number of Lin -ve cells in the liver ( Figure 3b ), which was reflected in downstream HSC LT s and CMPs ( Figure 3c ).…”

Section: Resultsmentioning

confidence: 99%

Neonatal hepatic myeloid progenitors expand and propagate liver inflammation in mice

Alkhani

Korsholm

Mohamedaly

et al. 2022

Preprint

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Background and Aims: Biliary atresia is a rapidly progressive pediatric inflammatory disease of the liver that leads to cirrhosis and necessitates liver transplantation. The rapid progression from liver injury to fulminant liver failure in children with biliary atresia suggests that factors specific to the perinatal hepatic environment are important for disease propagation. Hematopoietic stem and progenitor cells (HSPCs) serve as central hubs of inflammation and rely on inflammatory signals for their emigration from the liver to the bone marrow in neonatal mice. We hypothesized that HSPCs are critical for the propagation of perinatal liver inflammation (PLI). Methods: Newborn BALB/c mice were injected intraperitoneally with 1.5x106 focus forming units of Rhesus Rotavirus (RRV) to induce PLI or with PBS as control. Livers from RRV and PBS-injected mice were compared using histology and flow cytometry. To determine the effects of HSPCs on perinatal inflammation, RRV-infected neonatal mice were injected with anti-CD47 and anti-CD117 to deplete HSPCs. Results: RRV-induced PLI led to a significant increase in the number of common myeloid progenitors (Flt3+ CMPs: PBS=4426+247.2 vs RRV=9856+2009, p=0.0316; Flt3- CMPs: PBS=3063+254.9 vs RRV=9743+1539, p=0.0012). We corroborated these findings by observing a significant increase in CD34+ hematopoietic progenitors/cm2 in histological sections of RRV-infected livers (PBS=4.977+2.573 vs RRV=27.09+12.49, p=0.0075). Elimination of progenitors through antibody-mediated myeloablation rescued animals from PLI and significantly increased survival (RRV+isotype control 55.56% vs RRV+myeloablation 94.12%, Chi test=0.01). Conclusions: These data demonstrate that RRV causes expansion of HSPCs and propagates PLI. Targeting of HSPCs may be useful in preventing and treating neonatal inflammatory diseases of the liver like biliary atresia.

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“…This proposition is made because some Ly6C + cells are apoptosis-prone populations [ 57 ]. Ly6C + immune cells are also known to perform both proinflammatory and immunosuppressive functions [ 58 , 59 ]. As the EBIS is considered a fine-tuned inflammatory as well as an immunosuppressive area, it is expected that Ly6C + decidual cells may behave like local innate immune cells with pro-inflammatory and immunosuppressive roles supportive of embryonic survival.…”

Section: Discussionmentioning

confidence: 99%

Maternal Neutrophil Depletion Fails to Avert Systemic Lipopolysaccharide-Induced Early Pregnancy Defects in Mice

Panja¹,

Benjamin²,

Paria³

2021

IJMS

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Maternal infection-induced early pregnancy complications arise from perturbation of the immune environment at the uterine early blastocyst implantation site (EBIS), yet the underlying mechanisms remain unclear. Here, we demonstrated in a mouse model that the progression of normal pregnancy from days 4 to 6 induced steady migration of leukocytes away from the uterine decidual stromal zone (DSZ) that surrounds the implanted blastocyst. Uterine macrophages were found to be CD206+ M2-polarized. While monocytes were nearly absent in the DSZ, DSZ cells were found to express monocyte marker protein Ly6C. Systemic endotoxic lipopolysaccharide (LPS) exposure on day 5 of pregnancy led to: (1) rapid (at 2 h) induction of neutrophil chemoattractants that promoted huge neutrophil infiltrations at the EBISs by 24 h; (2) rapid (at 2 h) elevation of mRNA levels of MyD88, but not Trif, modulated cytokines at the EBISs; and (3) dose-dependent EBIS defects by day 7 of pregnancy. Yet, elimination of maternal neutrophils using anti-Ly6G antibody prior to LPS exposure failed to avert LPS-induced EBIS defects allowing us to suggest that activation of Tlr4-MyD88 dependent inflammatory pathway is involved in LPS-induced defects at EBISs. Thus, blocking the activation of the Tlr4-MyD88 signaling pathway may be an interesting approach to prevent infection-induced pathology at EBISs.

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Ly6cLo non-classical monocytes promote resolution of rhesus rotavirus-mediated perinatal hepatic inflammation

Cited by 18 publications

References 51 publications

Ly6c as a New Marker of Mouse Blood Vessels: Qualitative and Quantitative Analyses on Intact and Ischemic Retinas

Ly6c as a New Marker of Mouse Blood Vessels: Qualitative and Quantitative Analyses on Intact and Ischemic Retinas

Neonatal hepatic myeloid progenitors expand and propagate liver inflammation in mice

Maternal Neutrophil Depletion Fails to Avert Systemic Lipopolysaccharide-Induced Early Pregnancy Defects in Mice

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