October 20, 2026 – A study published in the Journal of Experimental Medicine by the lab of Silvia Monticelli at Institute for Research in Biomedicine (IRB) in Bellinzona, affiliated with USI, in collaboration with the lab of Gioacchino Natoli at IEO, reveals how genetic variants associated with autoimmune disease alter SKAP2 expression and in turn, T cell responses.
Even small differences in our genome can influence responses by the immune system, and many of these genetic variants can be associated with immune-mediated diseases. However, understanding how they alter immune cell functions remains a major challenge.
In a study published in the Journal of Experimental Medicine, researchers at IRB and IEO (Milan, Italy) investigated a region of the genome containing genetic variants associated with Crohn’s and other autoimmune diseases. They found that T lymphocytes carrying the risk-associated genetic variant express higher levels of SKAP2, a protein whose function in T cells had not been previously explored.
By combining the study of genetically selected T cells with experimental modulation of SKAP2 expression, the team showed that SKAP2 is required to control how T cells interact with other immune cells and with their surrounding environment. In particular, SKAP2 expression promoted T cell adhesion while simultaneously opposing their migration.
This study therefore connects disease-associated genetic variation to a specific molecular and cellular mechanism in human T cells. These findings provide insights for understanding how even relatively subtle differences in gene regulation can ultimately influence T cell responses, potentially leading to immune-mediated disease.
Mara Spinella, first author of this study says: “I was fascinated by how small differences in DNA can influence the way our immune system responds”.
Link to the Scientific Article:
A genetically regulated SKAP2 switch modulates human T lymphocyte adhesion and migration.
Spinella, M. C., F. Gualdrini, C. Leoni, J. S. Low, S. Polletti, A. Kenyon, S. Mauri, V. Vallelonga, M. Mostanfar, M. Pecoraro, C. Soriani, R. Marzi, E. Grassi, F. Bedin, E. Foli, N. Bianchi, E. Dzafo, S. Jovic, A. Cuomo, S. Rodighiero, D. Jarrossay, F. Sallusto, G. Natoli and S. Monticelli
J Exp Med. (2026) 223
Genetic variants associated with Crohn’s disease are linked to increased SKAP2 expression in T cells, which in turn regulates T cell responses.
