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Blanco Carrasco, Antonio JesusAuthorSalas Perdomo, Angelica MariaAuthorBlanco JAuthorBassolas-Molina HAuthorSalas AAuthorSerra PAuthorSantamaria PCorresponding Author

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Article

A Gut Microbial Mimic that Hijacks Diabetogenic Autoreactivity to Suppress Colitis

Publicated to:Cell. 171 (3): 655-+ - 2017-10-19 171(3), DOI: 10.1016/j.cell.2017.09.022

Authors: Nanjundappa, Roopa Hebbandi; Ronchi, Francesca; Wang, Jinguo; Clemente-Casares, Xavier; Yamanouchi, Jun; Umeshappa, Channakeshava Sokke; Yang, Yang; Blanco, Jesus; Bassolas-Molina, Helena; Salas, Azucena; Khan, Hamza; Slattery, Robyn M; Wyss, Madeleine; Mooser, Catherine; Macpherson, Andrew J; Sycuro, Laura K; Serra, Pau; McKay, Derek M; McCoy, Kathy D; Santamaria, Pere

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Abstract

The gut microbiota contributes to the development of normal immunity but, when dysregulated, can promote autoimmunity through various non-antigen-specific effects on pathogenic and regulatory lymphocytes. Here, we show that an integrase expressed by several species of the gut microbial genus Bacteroides encodes a low-avidity mimotope of the pancreatic ? cell autoantigen islet-specific glucose-6-phosphatase-catalytic-subunit-related protein (IGRP206-214). Studies in germ-free mice monocolonized with integrase-competent, integrase-deficient, and integrase-transgenic Bacteroides demonstrate that the microbial epitope promotes the recruitment of diabetogenic CD8+ T cells to the gut. There, these effectors suppress colitis by targeting microbial antigen-loaded, antigen-presenting cells in an integrin ?7-, perforin-, and major histocompatibility complex class I-dependent manner. Like their murine counterparts, human peripheral blood T cells also recognize Bacteroides integrase. These data suggest that gut microbial antigen-specific cytotoxic T cells may have therapeutic value in inflammatory bowel disease and unearth molecular mimicry as a novel mechanism by which the gut microbiota can regulate normal immune homeostasis. PAPERCLIP.Copyright © 2017 Elsevier Inc. All rights reserved.

Keywords

avidity maturationbacteroides integrasecommensalcytotoxic t cellsgenerationgerm-free micehelper-cellsinflammationinflammatory bowel diseaseislet-specific glucose 6-phosphatase catalytic subunit-related protein (igrp)nod micenonobese diabetic micerecognitionresponsesAdultAnimalsAutoantigensBacteroidesBacteroides integraseColitisCytotoxic t cellsCytotoxic t cellsFemaleG6pc2 protein, humanG6pc2 protein, mouseGastrointestinal microbiomeGerm-free miceGlucose-6-phosphataseHumansInflammatory bowel diseaseIslet-specific glucose 6-phosphatase catalytic subunit-related protein (igrp)Lymphoid tissueMaleMiceMice, inbred balb cMice, inbred nodMiddle agedMolecular mimicryRegulatory t-cellsT-lymphocytes

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Cell 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, 2017, it was in position 3/190, thus managing to position itself as a Q1 (Primer Cuartil), in the category Cell Biology. Notably, the journal is positioned above the 90th percentile.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 2.5. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Weighted Average of Normalized Impact by the Scopus agency: 2.2 (source consulted: FECYT Feb 2024)
  • Field Citation Ratio (FCR) from Dimensions: 10.29 (source consulted: Dimensions Jun 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-06-05, the following number of citations:

  • WoS: 90
  • Scopus: 97
  • Europe PMC: 69
  • Google Scholar: 113
  • OpenCitations: 94

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 2025-06-05:

  • 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: 327.
  • 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: 326 (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: 195.38.
  • The number of mentions on the social network Facebook: 4 (Altmetric).
  • The number of mentions on the social network X (formerly Twitter): 192 (Altmetric).

Leadership analysis of institutional authors

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

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

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