Evidence mapPaperPMID 41522693Full record

ArticlePNAS nexus2026

Soluble CD14 promotes Th17 expansion and differentiation through gamma-aminobutyric acid and expands infidel innate lymphoid cells.

Shima Shahbaz, Amirhossein Rahmati, Hussain Syed, Shokrollah Elahi

Erratum issuedAbstract read
In one paragraph

Article in PNAS nexus, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors.

Shima ShahbazDivision of Foundational Sciences, Mike Petryk School of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada T6G 2E1.
Amirhossein RahmatiDivision of Foundational Sciences, Mike Petryk School of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada T6G 2E1.ORCID https://orcid.org/0009-0003-5199-2337
Hussain SyedDivision of Gastroenterology, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada T6G 2E1.
Shokrollah ElahiDivision of Foundational Sciences, Mike Petryk School of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada T6G 2E1.ORCID https://orcid.org/0000-0002-7215-2009

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Interleukin-17 (IL-17) plays a central role in the pathogenesis of various autoimmune diseases. Soluble CD14 (sCD14), a marker of innate immune activation, is elevated in several inflammatory conditions. However, its influence on IL-17 production and the differentiation of Th17 cells remains poorly understood. We found that sCD14 enhances Th17-associated cytokine production and up-regulates critical transcription factors such as STAT3 and RORC. Notably, sCD14's effect on Th17 polarization was mediated indirectly through autologous sCD14-treated peripheral blood mononuclear cell (PBMC) supernatant (sCD14-PBMC-Sup). Additionally, we identified a distinct cytokine profile enriched for pro-inflammatory cytokines and chemokines in sCD14-treated T cells, further reinforcing the Th17-promoting role of sCD14. Interestingly, gamma-aminobutyric acid (GABA), a metabolite elevated in sCD14-treated monocytes, was identified as a potential contributor to Th17 polarization. GABA supplementation in T-cell cultures enhanced IL-17A secretion, indicating its role as a signaling molecule in T-cell differentiation. Our findings also revealed the expansion of innate lymphoid cell (ILC)2/3-like cells in T-cell cultures exposed to sCD14-PBMC-Sup and GABA, highlighting the potential role of monocytes in Th17-mediated immunity. Furthermore, while sCD14 promoted Th17 polarization, it simultaneously impaired T-cell activation and proliferation, suggesting an immunosuppressive effect mediated by soluble factors released from monocytes. These results underscore the dual role of sCD14 in modulating T-cell responses, promoting Th17 differentiation while suppressing T-cell effector functions. This study identifies a previously unrecognized role for sCD14 in promoting Th17 induction, highlighting its contribution to immune regulation and its potential as a therapeutic target in Th17-driven autoimmune conditions. Classification: Immunology.

Indexed as

4-aminobutyrategamma-aminobutryic acid (GABA)innate lymphoid cellslong COVIDSARS-CoV-2

Identifiers

PMID41522693
PMCPMC12781096

What Socratic holds

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Registered trials

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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 Socratic graph.