Vitamin A mediates conversion of monocyte-derived macrophages into tissue-resident macrophages during alternative activation

Gundra, Uma Mahesh; Girgis, Natasha; Gonzalez, Michael; Tang, Mei; Zande, Hendrik J. P. van der; Lin, Jian-Da; Ouimet, Mireille; Lily, J; Poles, Jordan; Vozhilla, Nicollaq; Fisher, Edward A.; Moore, Kathryn J.; Loke, P’ng

doi:10.1038/ni.3734

Cited by 129 publications

(142 citation statements)

References 48 publications

(73 reference statements)

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“…Thus, these results demonstrate that liver CD11b hi Mϕ have a BM origin, therefore emerging from recruited Ly6C hi monocytes. Interestingly, a small but significant fraction of CD11b lo resident Mϕ acquired a chimerism of BM origin which suggests, as recently proposed, that some recruited CD11b hi Mϕ could potentially convert into resident Mϕ [17]. [12,18].…”

Section: Ly6c Hi Monocytes Convert Into Cd11b Hi Mϕ After S Mansonimentioning

confidence: 60%

Recruitment of hepatic macrophages from monocytes is independent of IL‐4Rα but is associated with ablation of resident macrophages in schistosomiasis

et al. 2019

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Alternatively activated Mϕs (AAMϕ) accumulate in hepatic granulomas during schistosomiasis and have been suggested to originate in the bone marrow. What is less understood is how these Mϕ responses are regulated after S. mansoni infection. Here, we investigated the role of IL-4 receptor α-chain (IL-4Rα)-signalling in the dynamics of liver Mϕ responses. We observed that IL-4Rα signalling was dispensable for the recruitment of Ly6C hi monocytes and for their conversion into F4/80 hi CD64 hi CD11b hi Mϕ. Moreover, while IL-4Rα provided an AAMϕ phenotype to liver F4/80 hi CD64 hi CD11b hi Mϕ that was associated with regulation of granuloma formation, it was dispensable for host survival. Resident F4/80 hi CD64 hi CD11b lo Mϕ did not upregulate the AAMϕ signature gene Ym1. Rather, resident Mϕ nearly disappeared by week 8 after infection and artificial ablation of resident Mϕ in CD169 DTR mice did not affect the response to S. mansoni infection. Interestingly, ablation of CD169 + cells in naive mice resulted in the accumulation of F4/80 hi CD64 hi CD11b hi Mϕ, which was amplified when ablation occurred during schistosomiasis. Altogether, our results suggest the ablation of resident KCs after S. mansoni infection to be associated with the recruitment and accumulation of F4/80 hi CD64 hi CD11b hi Mϕ with lyz2-dependent IL-4Rα contributing to the regulation of granuloma inflammation but being dispensable for host survival.Keywords: liver r monocytes r mouse model r Mϕ r schistosomiasis See accompanying Commentary by Rückerl and CookAdditional supporting information may be found online in the Supporting Information section at the end of the article. infected with Schistosoma mansoni develop a severe liver pathology with granulomatous inflammatory responses directed toward the parasite eggs. During chronic infections, type 2 inflammation in the liver results in fibrosis, which leads to portal hypertension, bleeding from collateral vessels and ultimately death [2][3][4]. Mϕ accumulate in the liver and are a key cellular component in granuloma formation and host protection [2,5].Mϕ are plastic cells that can be alternatively activated by IL-4 and IL-13 via the type I or type II IL-4 receptor, respectively [6].

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Section: Ly6c Hi Monocytes Convert Into Cd11b Hi Mϕ After S Mansonimentioning

confidence: 60%

Recruitment of hepatic macrophages from monocytes is independent of IL‐4Rα but is associated with ablation of resident macrophages in schistosomiasis

et al. 2019

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“…They also demonstrated that GATA6 was a specific transcription factor for LPM development and maintenance. Recent work also suggested that vitamin A mediated the conversion of monocytes‐derived macrophages into tissue‐resident macrophages during alternative activation (Gundra et al, ). This brought new light to the association and alteration of monocytes, SPMs and LPMs in the inflammatory environment.…”

Section: Origins and Development Of Tissue‐resident Macrophagesmentioning

confidence: 99%

The origins and homeostasis of monocytes and tissue‐resident macrophages in physiological situation

Zhao

Zou

Du³

et al. 2018

Journal Cellular Physiology

126

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Monocytes and macrophages are critical effectors and regulators of innate immune response. They not only play crucial and distinctive roles in homeostasis, but also contribute to some pathologic processes. The heterogeneity of the macrophage lineage has been widely recognized and, in part, is a result of the specialization of resident macrophages in particular tissue microenvironments. Monocytes are usually known to originate in the bone marrow from a common myeloid progenitor that is shared with neutrophils, and they are then released into the peripheral blood. However, the origin of tissue-resident macrophages, crucial for homeostasis and immunity, has remained controversial until recently. During embryonic organogenesis, macrophages derived from yolk sac and fetal liver precursors are seeded throughout tissues, persisting in the adulthood as resident, self-maintaining populations. After birth, bone marrow-derived monocytes can replenish tissue resident macrophages following injury, infection and inflammation. In this review, we will mainly summarize our current understanding on the origin, ontogeny and fates of tissue macrophages and will briefly discuss the molecular regulation of resident macrophage homeostasis in physiological situation.

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“…These macrophages, originating from the peritoneal cavity, expressed M2 markers Arginase and RELMα, and exhibited a reparative function when recruited to the liver . While tissue‐resident macrophages are likely more rapid responders to injury, monocytes recruited from the blood can also differentiate into M2 macrophages and contribute to tissue repair following Schistosoma mansoni infection‐induced liver injury . This process was impaired in vitamin A‐deficient mice suggesting that dietary components are important for optimal M2 macrophage activation.…”

Section: Wound‐healing Macrophage Activation and Functionmentioning

confidence: 99%

Macrophages in wound healing: activation and plasticity

2019

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Macrophages are critically involved in wound healing, from dampening inflammation to clearing cell debris and coordinating tissue repair. Within the wound, the complexity of macrophage function is increasingly recognized, with adverse outcomes when macrophages are inappropriately activated, such as in fibrosis or chronic non‐healing wounds. Recent advances in in vivo and translational wound models, macrophage‐specific deletions and new technologies to distinguish macrophage subsets, have uncovered the vast spectrum of macrophage activation and effector functions. Here, we summarize the main players in wound‐healing macrophage activation and function, including cytokines, apoptotic cells, nucleotides and mechanical stimuli. We highlight recent studies demonstrating cooperation between these factors for optimal wound healing. Next, we describe recent technologies such as cell tracking and single‐cell RNA‐seq, which have uncovered remarkable plasticity and heterogeneity in blood‐derived or tissue‐resident macrophages and discuss the implications for wound healing. Lastly, we evaluate macrophage dysfunction in aberrant wound healing that occurs in aging, diabetes and fibrosis. A better understanding of the longevity and plasticity of wound‐healing macrophages, and identification of unique macrophage subsets or specific effector molecules in wound healing, would shed light on the therapeutic potential of manipulating macrophage function for optimal wound healing.

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Vitamin A mediates conversion of monocyte-derived macrophages into tissue-resident macrophages during alternative activation

Cited by 129 publications

References 48 publications

Recruitment of hepatic macrophages from monocytes is independent of IL‐4Rα but is associated with ablation of resident macrophages in schistosomiasis

Recruitment of hepatic macrophages from monocytes is independent of IL‐4Rα but is associated with ablation of resident macrophages in schistosomiasis

The origins and homeostasis of monocytes and tissue‐resident macrophages in physiological situation

Macrophages in wound healing: activation and plasticity

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