Evidence map›Paper›PMID 40508140›Full record

ArticleInternational journal of molecular sciences2025

Pro-Resolving Macrophage-Induced IL-35

Guoqin Cao, Takumi Memida, Shengyuan Huang, Elaheh Dalir Abdolahinia, Sunniva Ruiz, Sahar Hassantash, Jayant Ari, Satoru Shindo, Jiang Lin, Toshihisa Kawai and 1 more

Abstract read
In one paragraph

Article in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Review
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

11 authors.

Guoqin CaoDepartment of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, 3200 South University Drive, Fort Lauderdale, FL 33328, USA.
Takumi MemidaDepartment of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, 3200 South University Drive, Fort Lauderdale, FL 33328, USA.ORCID 0009-0004-9524-9462
Shengyuan HuangDepartment of Stomatology, Beijing Tongren Hospital, Capital Medical University, Beijing 100005, China.
Elaheh Dalir AbdolahiniaDepartment of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, 3200 South University Drive, Fort Lauderdale, FL 33328, USA.
Sunniva RuizDepartment of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, 3200 South University Drive, Fort Lauderdale, FL 33328, USA.
Sahar HassantashDepartment of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, 3200 South University Drive, Fort Lauderdale, FL 33328, USA.
Jayant AriDepartment of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, 3200 South University Drive, Fort Lauderdale, FL 33328, USA.
Satoru ShindoDepartment of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, 3200 South University Drive, Fort Lauderdale, FL 33328, USA.
Jiang LinDepartment of Stomatology, Beijing Tongren Hospital, Capital Medical University, Beijing 100005, China.
Toshihisa KawaiDepartment of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, 3200 South University Drive, Fort Lauderdale, FL 33328, USA.
Xiaozhe HanDepartment of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, 3200 South University Drive, Fort Lauderdale, FL 33328, USA.ORCID 0000-0001-8357-1471

Funding

Regulatory B Cells in the Amelioration of Immune-Mediated Periodontal DiseaseR01DE025255 · NIDCR · NOVA SOUTHEASTERN UNIVERSITY · PI HAN, XIAOZHE · 2015 to 2025
$5.8M
Role of OC-STAMP expressed on human osteoclasts in periodontitisR01DE029709 · NIDCR · NOVA SOUTHEASTERN UNIVERSITY · PI KAWAI, TOSHIHISA · 2020 to 2025
$2.8M
National Institutes of Dental and Craniofacial Research DE025255 and DE029709NIDCR NIH HHS R01 DE025255NIDCR NIH HHS R01 DE029709
6 · The paper itself

Abstract

The interaction between immune regulatory cells, such as regulatory B cells (Breg) and pro-resolving macrophages (M2 macrophages), plays an important role in the restoration of immune homeostasis during inflammation. PD-L1 is one of the effector molecules that mediates the immune regulation function of M2 macrophages. The activation of PD-L1/PD-1 signaling promotes the differentiation of Breg. Previous studies have shown that Breg promoted M2 macrophage polarization and enhanced their function, but little is known about the regulatory function of M2 macrophages on Breg differentiation. This study aims to determine the effect of M2 macrophages on Breg induction and the potential mechanism in vitro. Bone-marrow-derived macrophages were isolated from wild-type (WT) mice and polarized into M2 using IL-4/IL-13. To investigate the role of PD-L1/PD-1 in M2 macrophage-induced Breg differentiation, spleen B cells were isolated from WT or PD-1 knockout (KO) mice and co-cultured with either naïve (M0) or M2 macrophages for 48 h with or without trans-well inserts. The expression of IL-10, IL-35, and TGF-β1 in B cells was evaluated by flow cytometry and immunofluorescence staining. Recombinant PD-L1 was used to stimulate activated B cells, followed by the detection of IL-35 and TGF-β1. The results show that there was no significant difference in IL-10 expression among all groups. However, IL-35 and TGF-β1 expression in B cells was significantly increased in the M2+B, but not in M0+B, compared to B cells alone. Notably, such increases were diminished when M2 and B cells were separated by trans-well inserts. IL-35 expression was not significantly changed when B cells from PD-1 KO mice were co-cultured with M2 compared to the control. However, TGF-β1 expression was significantly increased when PD-1 KO B cells were co-cultured with M2 compared to the control. IL-35 expression in activated B cells was increased upon stimulation with PD-L1. However, TGF-β1 expression in activated B cells was increased regardless of the PD-L1 availability. This study demonstrates that pro-resolving macrophage-induced IL-35

Indexed as

B7-H1 AntigenB-Lymphocytes, RegulatoryInterleukinsLymphocyte ActivationMacrophagesProgrammed Cell Death 1 ReceptorTransforming Growth Factor beta1AnimalsCell DifferentiationMiceMice, Inbred C57BLMice, KnockoutSignal TransductionB7-H1 AntigenCd274 protein, mouseinterleukin-35, mouseInterleukinsPdcd1 protein, mouseProgrammed Cell Death 1 ReceptorTransforming Growth Factor beta1interleukin 35macrophagePD-L1regulatory B cellTGF-beta

Identifiers

PMID40508140
PMCPMC12155292

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.