Fractalkine–CX3CR1-dependent recruitment and retention of human CD1c+ myeloid dendritic cells by in vitro–activated proximal tubular epithelial cells

Kassianos, Andrew J.; Wang, Xiangju; Sampangi, Sandeep; Afrin, Sadia; Wilkinson, Rachel; Healy, Helen

doi:10.1038/ki.2014.407

Cited by 42 publications

(38 citation statements)

References 49 publications

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“…As an example, the chemokine receptor, CX3CR1 , which was uniquely upregulated by the DC clade (Fig. 6D), is also highly expressed by resident renal BDCA1 + DC (87). Overall, Langerin + , BDCA1 + CD14 + , and BDCA1 + CD14 − DC are the “true DC” of the human airways that can be separated transcriptionally from AM, CD14 + BDCA1 − DC, and CD14 − BDCA1 − DC of the MΦ clade.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Classification and Functional Characterization of Human Airway Macrophage and Dendritic Cell Subsets

Patel

Booth

Duggan

et al. 2017

The Journal of Immunology

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The respiratory system is a complex network of many cell types, including subsets of macrophages and dendritic cells that work together to maintain steady-state respiration. Due to limitations in acquiring cells from healthy human lung, these subsets remain poorly characterized transcriptionally and phenotypically. We set out to systematically identify these subsets in human airways by developing a schema of isolating large numbers of cells by whole lung bronchoalveolar lavage. Six subsets of phagocytic antigen presenting (HLA-DR+) cells were consistently observed. Aside from alveolar macrophages, subsets of Langerin+, BDCA1− CD14+, BDCA1+ CD14+, BDCA1+ CD14−, and BDCA1− CD14− cells were identified. These subsets varied in their ability to internalize Escherichia coli, Staphylococcus aureus, and Bacillus anthracis particles. All subsets were more efficient at internalizing S. aureus and B. anthracis compared to E. coli. Alveolar macrophages and CD14+ cells were overall more efficient at particle internalization compared to the four other populations. Subsets were further separated into two groups based on their inherent capacities to upregulate surface CD83, CD86, and CCR7 expression levels. Whole genome transcriptional profiling revealed a clade of “true dendritic cells” consisting of Langerin+, BDCA1+ CD14+, and BDCA1+ CD14− cells. The dendritic cell clade was distinct from a macrophage/monocyte clade, as supported by higher mRNA expression levels of several dendritic cell-associated genes, including CD1, FLT3, CX3CR1, and CCR6. Each clade, and each member of both clades, were discerned by specific upregulated genes, which can serve as markers for future studies in healthy and diseased states.

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Section: Discussionmentioning

confidence: 99%

Transcriptional Classification and Functional Characterization of Human Airway Macrophage and Dendritic Cell Subsets

Patel

Booth

Duggan

et al. 2017

The Journal of Immunology

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“…23 Both CXCR3 and CX3CR1 have been implicated in human tubulointerstitial injury and loss of kidney function. 36,37 It is thus tempting to speculate that these chemokine receptors are pivotal in NK cell recruitment and retention in human CKD.…”

Section: Discussionmentioning

confidence: 99%

“…26 The proinflammatory roles of IFN-g in kidney disease include the following: (i) M1 macrophage activation, 39 (ii) modulation of effector T-cell responses, 40 (iii) induction of major histocompatibility complex class I and II molecules for antigen presentation, 41 and (iv) upregulation of chemokines that augment immune cell infiltration. 37 In addition to its proinflammatory effects, IFN-g has also been reported to limit kidney disease progression and preserve renal function. [42][43][44] These studies highlight the complex nature of IFN-g dependent on the context of the kidney disease process.…”

Section: Discussionmentioning

confidence: 99%

Interferon-γ production by tubulointerstitial human CD56bright natural killer cells contributes to renal fibrosis and chronic kidney disease progression

Law

Wilkinson

Wang

et al. 2017

Kidney International

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Natural killer (NK) cells are a population of lymphoid cells that play a significant role in mediating innate immune responses. Studies in mice suggest a pathological role for NK cells in models of kidney disease. In this study, we characterized the NK cell subsets present in native kidneys of patients with tubulointerstitial fibrosis, the pathological hallmark of chronic kidney disease. Significantly higher numbers of total NK cells (CD3CD56) were detected in renal biopsies with tubulointerstitial fibrosis compared with diseased biopsies without fibrosis and healthy kidney tissue using multi-color flow cytometry. At a subset level, both the CD56 NK cell subset and particularly the CD56 NK cell subset were elevated in fibrotic kidney tissue. However, only CD56 NK cells significantly correlated with the loss of kidney function. Expression of the tissue-retention and -activation molecule CD69 on CD56 NK cells was significantly increased in fibrotic biopsy specimens compared with non-fibrotic kidney tissue, indicative of a pathogenic phenotype. Further flow cytometric phenotyping revealed selective co-expression of activating receptor CD335 (NKp46) and differentiation marker CD117 (c-kit) on CD56 NK cells. Multi-color immunofluorescent staining of fibrotic kidney tissue localized the accumulation of NK cells within the tubulointerstitium, with CD56 NK cells (NKp46 CD117) identified as the source of pro-inflammatory cytokine interferon-γ within the NK cell compartment. Thus, activated interferon-γ-producing CD56 NK cells are positioned to play a key role in the fibrotic process and progression to chronic kidney disease.

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“…With injury, macrophages are recruited through the production of inflammatory cytokines such as MCP-1 67 and fractalkine 68 to remove debris and permit regeneration. 69 Interrupting adhesion molecule expression decreases this recruitment.…”

Section: The Pathophysiology Of Progressive Ckdmentioning

confidence: 99%

The Tubulointerstitial Pathophysiology of Progressive Kidney Disease

Schnaper

2017

Advances in Chronic Kidney Disease

115

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Accumulating evidence suggests that the central locus for the progression of chronic kidney disease (CKD) is the renal proximal tubule. As injured tubular epithelial cells dedifferentiate in attempted repair they stimulate inflammation and recruit myofibroblasts. At the same time, tissue loss stimulates remnant nephron hypertrophy. Increased tubular transport workload eventually exceeds the energy-generating capacity of the hypertrophied nephrons, leading to anerobic metabolism, acidosis, hypoxia, endoplasmic reticulum stress and the induction of additional inflammatory and fibrogenic responses. The result is a vicious cycle of injury, misdirected repair, maladaptive responses and more nephron loss. Therapy that might be advantageous at one phase of this progression pathway could be deleterious during other phases. Thus, interrupting this downward spiral requires narrowly targeted approaches that promote healing and adequate function without generating further entry into the progression cycle.

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Fractalkine–CX3CR1-dependent recruitment and retention of human CD1c+ myeloid dendritic cells by in vitro–activated proximal tubular epithelial cells

Cited by 42 publications

References 49 publications

Transcriptional Classification and Functional Characterization of Human Airway Macrophage and Dendritic Cell Subsets

Transcriptional Classification and Functional Characterization of Human Airway Macrophage and Dendritic Cell Subsets

Interferon-γ production by tubulointerstitial human CD56bright natural killer cells contributes to renal fibrosis and chronic kidney disease progression

The Tubulointerstitial Pathophysiology of Progressive Kidney Disease

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