{rfName}

Indexed in

License and use

Icono OpenAccess

Citations

Altmetrics

Grant support

The author(s) declarefinancial support was received for theresearch, authorship, and/or publication of this article. This workwas supported in part by Genome Canada and Genome Alberta (GAPP program), the Canadian Institutes of Health Research (CIHR) (FDN-353029, PJT-479040, PJT-479038, FRN-168480 (with JDRF), DT4-179512), the European Union (HORIZON-HLTH-2022,project 101076383-PHOENIX-), Ministerio de Ciencia e Innovacion of Spain (MCIN; PID2021-125493OB-I00), Generalitatde Catalunya (SGR and CERCA Programmes) and Red Espanola de Supercomputacion (RES, providing CSUC resources). JM, JG and PS were supported by predoctoral studentship from FPU (MINECO). PS e was an investigator of the Ramon y Cajal reintegration program and was supported by a JDRF Career Development Award.

Analysis of institutional authors

Garnica, JosepAuthorMoro, JoelAuthorSole, PatriciaAuthorSerra, PauAuthorSantamaria, PereCorresponding Author

Share

Publications
>
Article

Transcriptional re-programming of liver-resident iNKT cells into T-regulatory type-1-like liver iNKT cells involves extensive gene de-methylation

Publicated to:Frontiers In Immunology. 15 1454314- - 2024-09-09 15(), DOI: 10.3389/fimmu.2024.1454314

Authors: Montaño, J; Garnica, J; Moro, J; Solé, P; Serra, P; Santamaria, P; Yamanouchi, J; Mondal, D; Yang, Y

Affiliations

Abstract

Unlike conventional CD4+ T cells, which are phenotypically and functionally plastic, invariant NKT (iNKT) cells generally exist in a terminally differentiated state. Na & iuml;ve CD4+ T cells can acquire alternative epigenetic states in response to different cues, but it remains unclear whether peripheral iNKT cells are epigenetically stable or malleable. Repetitive encounters of liver-resident iNKT cells (LiNKTs) with alpha-galactosylceramide (alpha GalCer)/CD1d-coated nanoparticles (NPs) can trigger their differentiation into a LiNKT cell subset expressing a T regulatory type 1 (TR1)-like (LiNKTR1) transcriptional signature. Here we dissect the epigenetic underpinnings of the LiNKT-LiNKTR1 conversion as compared to those underlying the peptide-major histocompatibility complex (pMHC)-NP-induced T-follicular helper (TFH)-to-TR1 transdifferentiation process. We show that gene upregulation during the LINKT-to-LiNKTR1 cell conversion is associated with demethylation of gene bodies, inter-genic regions, promoters and distal gene regulatory elements, in the absence of major changes in chromatin exposure or deposition of expression-promoting histone marks. In contrast, the na & iuml;ve CD4+ T cell-to-TFH differentiation process involves extensive remodeling of the chromatin and the acquisition of a broad repertoire of epigenetic modifications that are then largely inherited by TFH cell-derived TR1 cell progeny. These observations indicate that LiNKT cells are epigenetically malleable and particularly susceptible to gene de-methylation.

Keywords

Alpha galcer/cd1d-coated nanoparticlesAlpha-galactosylceramideAnimalsAntigens, cd1dBindingCell differentiationChromatinDemethylationDifferentiationDna methylationEpigenesis, geneticEpigeneticEpigenetic controlEpigeneticsGalactosylceramidesGene de-methylationInkt cellInkt cell re-programmingLiverLiver inkt cellLiver inkt-regulatory type-1 (linktr1) cellsLocusMaintenanceMiceMice, inbred c57blNatural killer t-cellsR/bioconductor packageSpecificitT-lymphocytes, regulatoryTranscription, geneticΑgalcer/cd1d-coated nanoparticles

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Frontiers In Immunology due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2024 there are still no calculated indicators, but in 2023, it was in position 37/181, thus managing to position itself as a Q1 (Primer Cuartil), in the category Immunology.

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-06-04:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 6.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 6 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 2.85.
  • The number of mentions on the social network X (formerly Twitter): 3 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Canada.

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Montaño, Javier) and Last Author (Santamaria Vilanova, Pere).

the author responsible for correspondence tasks has been Santamaria Vilanova, Pere.