Altered antiviral pathways identified in an autoimmune disease

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

This finding, unprecedented in the study of this autoimmune disease, highlights a higher 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 on their membrane of activating molecules called MICab. These molecules are responsible for activating NK lymphocytes through the NKG2D receptor in patients with pSS.

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

“These interactions were confirmed both in vitro and in primary Sjögren's animal models,” the researchers emphasize.

New therapies against autoimmunity

In the field of therapies against autoimmunity, this discovery opens paths towards a better understanding of the cellular and molecular bases of certain inflammatory autoimmune diseases, the 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 treatments against pSS, 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. The predoctoral student Ildefonso Sánchez Cerrillo has carried out the analyzes in collaboration with the Rheumatology Service (Dr. Santos Castañeda, Dr. Isidoro Álvaro) 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, Aceña-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, Álvaro IG, Castañeda 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.

More scientific culture in UAM Gazette