Evidence map›Paper›PMID 42256442›Full record

ArticleJournal of extracellular biology2026

Extracellular Vesicle-Associated IL4 Displays Enhanced Anti-Inflammatory Properties in Microglial Cells.

Giulia Marostica, Chiara Frigè, Annamaria Finardi, Alessandra Mandelli, Susanna Manenti, Stella Siciliani, Paola Podini, Ivan De Curtis, Luca Muzio, Elena Rossi and 2 more

Abstract read
In one paragraph

Article in Journal of extracellular biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Giulia MarosticaInstitute of Experimental Neurology, Division of Neuroscience IRCCS Ospedale San Raffaele Milan Italy.
Chiara FrigèInstitute of Experimental Neurology, Division of Neuroscience IRCCS Ospedale San Raffaele Milan Italy.
Annamaria FinardiInstitute of Experimental Neurology, Division of Neuroscience IRCCS Ospedale San Raffaele Milan Italy.
Alessandra MandelliInstitute of Experimental Neurology, Division of Neuroscience IRCCS Ospedale San Raffaele Milan Italy.
Susanna ManentiInstitute of Experimental Neurology, Division of Neuroscience IRCCS Ospedale San Raffaele Milan Italy.
Stella SicilianiInstitute of Experimental Neurology, Division of Neuroscience IRCCS Ospedale San Raffaele Milan Italy.
Paola PodiniInstitute of Experimental Neurology, Division of Neuroscience IRCCS Ospedale San Raffaele Milan Italy.
Ivan De CurtisVita e Salute San Raffaele University Milan Italy.
Luca MuzioInstitute of Experimental Neurology, Division of Neuroscience IRCCS Ospedale San Raffaele Milan Italy.
Elena RossiInstitute of Experimental Neurology, Division of Neuroscience IRCCS Ospedale San Raffaele Milan Italy.
Paola de CandiaDepartment of Molecular Medicine and Medical Biotechnology University of Naples Federico II Naples Italy.ORCID https://orcid.org/0000-0003-4767-446X
Roberto FurlanInstitute of Experimental Neurology, Division of Neuroscience IRCCS Ospedale San Raffaele Milan Italy.ORCID https://orcid.org/0000-0001-7376-9425

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Neuroinflammation and neurodegeneration are strictly related phenomena, characterized by dysregulation of microglia, central nervous system (CNS) resident immune cells. Interleukin-4 (IL4) has shown beneficial abilities to re-establish microglial homeostasis in experimental models of CNS traumatic injury, stroke and multiple sclerosis, but its optimal administration system remains uncertain. Here, we show that extracellular vesicles (EVs) released by engineered murine microglia BV2 cells constitutively expressing IL4 induced a faster and enhanced anti-inflammatory phenotype in wild type BV2 cells (as assessed by IL4R downstream signalling), compared with soluble IL4. This effect was blunted by an anti-IL4 antibody, while it was not dampened by knocking out the IL4 receptor α subunit in EV-releasing BV2 cells, suggesting that IL4 was localized on the EV surface and did not necessitate to be co-conveyed with the receptor to exert its function. BV2 cells treated with EV-associated IL4, compared with soluble IL4, demonstrated delayed permanence of IL4R in the early endosome, suggesting amplified signalling effects. In conclusion, we here show that the association of IL4 with microglia-derived EVs improve its anti-inflammatory effect in an in vitro murine microglial model, which may inform on novel therapeutic opportunities to restore microglia in human disorders marked by neuroinflammation.

Indexed as

anti‐inflammatory effectBV2endosomal pathwayextracellular vesiclesIL4 receptorinterleukin‐4kinetic

Identifiers

PMID42256442
PMCPMC13238552

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.