Altered Antiviral Pathways Identified in Autoimmune Disease

Diagram of the cellular interactions described. Martin Gayo
Diagram of the cellular interactions described. Martin Gayo

A team from the Universidad Autónoma de Madrid (UAM) and the Hospital Universitario de la Princesa has identified previously unknown alterations in a subtype of immune system cells in patients with Sjögren’s syndrome. The finding, published in The EMBO Journal, could open up new avenues for the development of more specific and effective treatments against this chronic autoimmune disease.

A team of researchers from the Universidad Autónoma de Madrid (UAM) and the Hospital Universitario de la Princesa has discovered significant alterations in natural killer cells, known as NK (Natural Killer) cells, in patients with primary Sjögren’s disease (pSS).

This finding, unpublished in the study of this autoimmune disease, highlights an increased level of abnormal activation in NK cells, caused by their interaction with the dendritic cells of the immune system.

Through gene expression analysis, scientists have revealed that an aberrant activation of antiviral responses in dendritic cells leads to the expression of activating molecules called MICab on their membrane. These molecules are responsible for activating NK lymphocytes through the NKG2D receptor in pSS patients.

The results, published in The EMBO Journal, show that this interaction, hitherto unknown in the context of this disease, contributes significantly to the unusual activation of NK cells and their subsequent infiltration of the salivary glands, the organs affected in pSS.

"These interactions were confirmed both in vitro and in animal models of primary Sjögren’s," the researchers emphasize.

New therapies against autoimmunity

In the field of therapies against autoimmunity, this discovery opens the way to a better understanding of the cellular and molecular basis of certain inflammatory autoimmune diseases, knowledge of which is crucial for the development of more effective treatments.

The recent findings could facilitate the identification of new therapies specifically targeting cells involved in autoimmune diseases. "These new therapies could substantially improve current pSS treatments, which are often nonspecific and may have limited efficacy or cause unwanted side effects," the authors note.

The study has been led by the laboratory of Dr. Enrique Martín Gayo at the UAM and the Hospital Universitario de la Princesa. Predoctoral student Ildefonso Sánchez Cerrillo has carried out the analyses in collaboration with the Rheumatology Service (Dr. Santos Castańeda, Dr. Isidoro Élvaro) and Immunology (Dr. Francisco Sánchez Madrid) of this Hospital, and with teams from the National Center for Cardiovascular Research (Dr. Ana Dopazo and Dr. Almudena Ramiro).

Bibliographic reference:

Sánchez-Cerrillo I, Calzada-Fraile D, Triguero-Martínez A, Calvet-Mirabent M, Popova O, Delgado-Arévalo C, Valdivia-Mazeyra M, Ramírez-Huesca M, de Luis EV, Benguría A, Aceńa-Gonzalo T, Moreno-Vellisca R, de Llano MA, de la Fuente H, Tsukalov I, Delgado-Wicke P, Fernández-Ruiz E, Roy-Vallejo E, Tejedor-Lázaro R, Ramiro A, Iborra S, Sánchez-Madrid F, Dopazo A, Élvaro IG, Castańeda S, Martin-Gayo E. (2023). "MICa/b-dependent activation of natural killer cells by CD64+ inflammatory type 2 dendritic cells contributes to autoimmunity". EMBO J. 2023 Nov 2:e113714. doi: 10.15252/embj.2023113714. Online ahead of print. PMID: 37916875.

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