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Institute for Research in Biomedicine
Istituto di Ricerca in Biomedicina

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New study from the Uguccioni’s lab revealing the activity of the CXCL12/HMGB1 heterocomplex in sustaining inflammation in Rheumatoid Arthritis

on Tuesday, October 23, 2018

The group of Dr. Uguccioni has revealed the mechanism by which an heterocomplex formed between the chemokine CXCL12 and the alarmin HMGB1, which was discovered in the past by the group, is maintained in chronic inflammation, and in particular in Rheumatoid Arthritis (RA).

The activation of mechanisms counteracting the oxidative stress in the extracellular compartment preserves HMGB1 in its reduced form, favoring the heterocomplex formation and contributing to fuel the influx of inflammatory cells. The activity of the heterocomplex depends on disease activity, on the COX2 and JAK/STAT pathways, and is determined by the redox potential of the microenvironment. In RA, the presence of an active thioredoxin system correlates with the enhanced cell migration, and with the presence of the heterocomplex in the synovial fluid.

The study indicates that targeting the heterocomplex formation and its activity could be an additional tool for dampening the inflammation sustained by cell recruitment, in particular for those patients with chronic inflammatory conditions who poorly respond to current therapies.

Graphical abstract representing how the heterocomplex CXCL12/HMGB1 is maintained in active Rheumatoid Arthritis thanks to the activity of the Thioredoxin system. The panel was created using Servier Medical Art according to Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/). Changes were made to the original cartoons.

The discovery is the result of the joint effort of a team of researchers guided by Dr. Mariagrazia Uguccioni at the Institute for Research in Biomedicine, the Departments of Rheumatology of the William Harvey Institute (London, UK), the University of Pavia (Italy) and the University of Zurich (Switzerland), the San Raffaele Institute (Milan, Italy) and the San Martino Hospital (Genoa, Italy).  The study has been published in Frontiers in Immunology.

 

Article

Redox-Mediated Mechanisms Fuel Monocyte Responses to CXCL12/HMGB1 in Active Rheumatoid Arthritis.

Cecchinato, V., G. D'Agostino, L. Raeli, A. Nerviani, M. Schiraldi, G. Danelon, A. Manzo, M. Thelen, A. Ciurea, M. E. Bianchi, A. Rubartelli, C. Pitzalis and M. Uguccioni

Front Immunol. 2018; 9:2118.