Cell surface antigens of neonatal monocytes are selectively impaired in basal expression, but hyperresponsive to lipopolysaccharide and zymosan

Hikita, Norikatsu; Cho, Yuki; Tachibana, Daisuke; Hamazaki, Takashi; Koyama, Masayasu; Tokuhara, Daisuke

doi:10.1016/j.jri.2019.102614

Cited by 6 publications

(6 citation statements)

References 28 publications

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“…Adult CD14+++/CD16− monocytes demonstrated higher CD11b and lower LFA-1 and CD54, as compared to their own CD14dim/CD16+ counterparts. These results are in agreement with reports of reduced CD11b expression on cord blood monocytes 37,41,61 , including correlation with gestational age 6 , as well as those indicating increased CD31, CD54 and decreased CD11b levels on adult CD16+ monocytes as compared to their CD16− counterparts 62,63 . Of note, an increase of CD11b on circulating monocytes is a biomarker for late-onset sepsis in extremely low-birth-weight neonates 64 .…”

Section: Discussionsupporting

confidence: 92%

“…To further characterize the extravasation potential of human neonatal monocytes, we measured the cell surface expression of CD11b, CD31, CD49d, CD54, CD50 and LFA-1. These molecules represent the most ubiquitously reported adhesion molecules used by human monocytes to extravasate [37][38][39][40][41][42][43] . Among these markers, CD31 and CD11b demonstrated significantly lower levels on both the CD16− and CD16+ neonatal monocytes, as compared to their adult counterparts ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Considering that newborn monocytes could express a divergent set of surface anchoring molecules, used selectively to colonize healthy non-inflamed tissues, we assessed CD11b, CD31 (PECAM-1), CD49d, CD50 (ICAM-3), CD54 (ICAM-1) and LFA-1 (CD11a/CD18). These markers are important mediators of human monocyte extravasation [37][38][39][40][41][42][43] and are constitutively expressed on the surface of monocytes 60 . CD49d pairs with β1-integrin CD29 to form VLA-4, and CD11a and CD11b couple with β2 integrin CD18 to form LFA-1 and CR3, respectively.…”

Section: Discussionmentioning

confidence: 99%

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Neonatal monocytes demonstrate impaired homeostatic extravasation into a microphysiological human vascular model

Sánchez-Schmitz

Morrocchi

Cooney

et al. 2020

Sci Rep

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Infections are most frequent at the extremes of life, especially among newborns, reflecting age-specific differences in immunity. Monocytes maintain tissue-homeostasis and defence-readiness by escaping circulation in the absence of inflammation to become tissue-resident antigen presenting cells in vivo. Despite equivalent circulating levels, neonates demonstrate lower presence of monocytes inside peripheral tissues as compared to adults. To study the ability of monocytes to undergo autonomous transendothelial extravasation under biologically accurate circumstances we engineered a three-dimensional human vascular-interstitial model including collagen, fibronectin, primary endothelial cells and autologous untreated plasma. This microphysiological tissue construct enabled age-specific autonomous extravasation of monocytes through a confluent human endothelium in the absence of exogenous chemokines and activation. Both CD16− and CD16+ newborn monocytes demonstrated lower adherence and extravasation as compared to adults. In contrast, pre-activated tissue constructs were colonized by newborn monocytes at the same frequency than adult monocytes, suggesting that neonatal monocytes are capable of colonizing inflamed tissues. The presence of autologous plasma neither improved newborn homeostatic extravasation nor shaped age-specific differences in endothelial cytokines that could account for this impairment. Newborn monocytes demonstrated significantly lower surface expression of CD31 and CD11b, and mechanistic experiments using blocking antibodies confirmed a functional role for CD31 and CD54 in neonatal homeostatic extravasation. Our data suggests that newborn monocytes are intrinsically impaired in extravasation through quiescent endothelia, a phenomenon that could contribute to the divergent immune responsiveness to vaccines and susceptibility to infection observed during early life.

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Section: Discussionsupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Neonatal monocytes demonstrate impaired homeostatic extravasation into a microphysiological human vascular model

Sánchez-Schmitz

Morrocchi

Cooney

et al. 2020

Sci Rep

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“…39,40 However, after LPS treatment, expression of co-stimulatory molecules, MHC-II and CD80, does not differ significantly from adults. 41 Altered cellular metabolism is now emerging as a critical regulator of neonatal monocyte function, especially cytokine production. Whole-blood transcriptomic data suggest significantly increased activity in glucose and cholesterol metabolic pathways.…”

Section: Monocytes/macrophagesmentioning

confidence: 99%

“…While limiting innate immune responses, this reduced capacity to produce key cytokines along with reduced expression of human leukocyte antigen (HLA)‐DR and co‐stimulatory molecules such as CD40 at the basal state also affect the ability to activate T cells 39,40 . However, after LPS treatment, expression of co‐stimulatory molecules, MHC‐II and CD80, does not differ significantly from adults 41 . Altered cellular metabolism is now emerging as a critical regulator of neonatal monocyte function, especially cytokine production.…”

Section: Innate Immune Responsesmentioning

confidence: 99%

A role for metabolism in determining neonatal immune function

Holm

Jenkins

Cronin

et al. 2021

Pediatric Allergy Immunology

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Birth represents a relatively dramatic transition from an environment with a low microbial burden to one abundant in commensal and potentially pathogenic challenges that the neonatal immune system must be able to respond to. Immune responses in preterm and term neonates differ from those of adults, generally being characterized as diminished, tolerant or Th skewed although we must be mindful that these are highly evolved, stage of life appropriate responses.Efforts to clarify the phenotypes and mechanisms prevalent at this time are ongoing so that we can better understand the significance of differences at this stage of development for long-term health.The need to understand how the neonatal immune response differs to that of adults is driven by the mortality and morbidity associated with infection and sepsis in newborns and infants and the need for protective vaccine responses that can mitigate these.

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EGF-Receptor against Amphiregulin (AREG) Influences Costimulatory Molecules on Monocytes and T Cells and Modulates T-Cell Responses

Dreschers,

Platen,

Oppermann

et al. 2023

Journal of Immunology Research

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Amphiregulin (AREG) is a ligand of the epidermal growth factor receptor (EGFR) and has been shown to regulate the phagocytosis-induced cell death of monocytes in peripheral blood. AREG-dependent apoptotic signaling engages factors of the intrinsic and extrinsic apoptotic pathway, such as BCL-2, BCL-XL, and death ligand/receptor CD95/CD95L. Here, we tested the hypothesis that AREG influences costimulatory monocyte functions, which are crucial for T-cell responses. We found a stronger expression of AREG and EGFR in monocytes compared to lymphocytes. As a novel function of AREG, we observed reduced T-cell proliferation following polyclonal T-cell stimulation with OKT3. This reduction of proliferation occurred in the presence of monocytes as well as in their absence, monocyte signaling being replaced by crosslinking of OKT3. Increasing concentrations of AREG down-modulated the concentration of costimulatory B7 molecules (CD80/CD86) and HLA-DR on monocytes. In proliferation assays, CD28 expression on T cells was down-modulated on the application of OKT3 but unaltered by AREG. LcK activation, following OKT3-stimulation, was reduced in T cells that had been coincubated with AREG. The effects of AREG on T-cell phenotypes were also present when monocytes were depleted and OKT3 was crosslinked. The rearranged expression of immunological synapse proteins was accompanied by an alteration of T-cell polarization. Although the proportion of regulatory T cells was not shifted by AREG, IL-17-expressing T cells were significantly enhanced, with a bias toward TH1-polarization. Taken together, these results suggest that AREG acts as an immunoregulatory molecule at the interface between antigen-presenting cells and T cells.

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Cell surface antigens of neonatal monocytes are selectively impaired in basal expression, but hyperresponsive to lipopolysaccharide and zymosan

Cited by 6 publications

References 28 publications

Neonatal monocytes demonstrate impaired homeostatic extravasation into a microphysiological human vascular model

Neonatal monocytes demonstrate impaired homeostatic extravasation into a microphysiological human vascular model

A role for metabolism in determining neonatal immune function

EGF-Receptor against Amphiregulin (AREG) Influences Costimulatory Molecules on Monocytes and T Cells and Modulates T-Cell Responses

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