Evidence map›Paper›PMID 25959810›Full record

ArticleClinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology2015

Vitamins A and D have antagonistic effects on expression of effector cytokines and gut-homing integrin in human innate lymphoid cells.

B Ruiter, S U Patil, W G Shreffler

Open access · greenAbstract read
In one paragraph

Article in Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
2.9field-weighted citation impact, top 9% of its field
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

45 citing papers in PubMed, 67 citations in OpenAlex.

  1. Article
  2. Regulation of innate lymphoid cell by microbial metabolites.Journal of molecular medicine (Berlin, Germany) · 2025
    Review
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  8. Article
  9. Pet Wellness and Vitamin A: A Narrative Overview.Animals : an open access journal from MDPI · 2024
    Review
  10. Review
  11. Vitamin D and allergic diseases.Frontiers in immunology · 2024
    Review
  12. Article
  13. ILC3: a case of conflicted identity.Frontiers in immunology · 2023
    Review
  14. Review
  15. Review
  16. Article
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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

3 authors at 2 institutions in 1 country.

B RuiterCenter for Immunology & Inflammatory Diseases, Massachusetts General Hospital, Boston, MA, USA.
S U PatilCenter for Immunology & Inflammatory Diseases, Massachusetts General Hospital, Boston, MA, USA.
W G ShrefflerCenter for Immunology & Inflammatory Diseases, Massachusetts General Hospital, Boston, MA, USA.
Harvard University · USMassachusetts General Hospital · US

Funding

Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG · 1991 to 2026
$35.3M
ROLE OF DIETARY CONSTITUENTS ON GENE EXPRESSION IN INTESTINAL EPITHELIUMP30DK040561 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI Elizabeth Austen Lawson, Takara Leah Stanley · 1994 to 2026
$31.6M
Tetramer CoreU19AI095261 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI HAMILOS, DANIEL L. · 2011 to 2015
$10.8M
Translational Immunology Core's FACSAria Cell SorterS10RR023440 · NCRR · MASSACHUSETTS GENERAL HOSPITAL · PI PREFFER, FREDERIC IRA · 2008 to 2008
$500k
NCRR NIH HHS S10 RR023440NIAID NIH HHS U19 AI095261NIDDK NIH HHS P30 DK040561NIDDK NIH HHS P30 DK043351
6 · The paper itself

Abstract

backgroundRetinoic acid (RA), the main biologically active metabolite of vitamin A, is known to promote gut homing of lymphocytes, as well as various regulatory and effector immune responses. In contrast, the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D3), is predominantly immunosuppressive. Little is known about the direct effects of these vitamins on the recently identified innate lymphoid cells (ILCs).

objectiveWe sought to characterize the effects of RA and 1,25D3 on human ILCs.

methodsPeripheral blood mononuclear cells were isolated from 27 non-selected blood donor buffy coats, and ILCs were sorted by FACS. ILC1, ILC2, and ILC3 cells were cultured for 5 days with RA, 1,25D3, and various cytokines known to activate ILCs (IL-2, IL-7, IL-12, thymic stromal lymphopoietin (TSLP), IL-25, and IL-33). Cytokines produced by ILCs were measured in culture supernatants, and surface receptor expression was analysed by flow cytometry.

resultsRetinoic acid acted synergistically with IL-2 and other activating cytokines to induce expression of the gut-homing integrin α4β7 in ILCs, as well as production of IL-5 and IL-13 in ILC2 cells, and IFN-γ in ILC1 and ILC3 cells. Expression of integrin α4β7 and cytokine production in ILCs stimulated with RA + IL-2 was increased at least fourfold as compared to ILCs cultured with RA or IL-2 alone. In contrast, RA completely inhibited the IL-2-induced expression of cutaneous lymphocyte antigen (CLA) in ILCs. Moreover, addition of 1,25D3 to ILCs cultured with RA + IL-2 inhibited cytokine production and expression of integrin α4β7 by at least 30%.

conclusionsRetinoic acid and 1,25D3 have antagonistic effects on the expression of effector cytokines and gut-homing integrin by human ILCs. The balance between these vitamins may be an important factor in the functioning of ILCs and the diseases in which ILCs are implicated, such as allergic inflammation.

Indexed as

Cells, CulturedCytokinesDrug SynergismGene ExpressionHumansImmunity, InnateIntegrinsLymphocyte SubsetsVitamin AVitamin DCytokinesdihydroxy-vitamin D3integrin alpha4beta7IntegrinsVitamin AVitamin Dcytokinesgut-homing integrinHumanILC2innate lymphoid cellsvitamin Avitamin D

Identifiers

PMID25959810
PMCPMC4784097
OpenAlexW1932484161

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.