Open access
A genetically regulated SKAP2 switch modulates human T lymphocyte adhesion and migration
Mara Cetty Spinella
Francesco Gualdrini
Cristina Leoni
J. Low
S. Polletti
Amy Kenyon
S. Mauri
V. Vallelonga
Mehrpouya Mostanfar
M. Pecoraro
C. Soriani
Roberta Marzi
Elena Grassi
F. Bedin
Elena Foli
N. Bianchi
E. Džafo
Sandra Jovic
Alessandro Cuomo
S. Rodighiero
D. Jarrossay
F. Sallusto
Gioacchino Natoli
S. Monticelli
Medicine
Abstract
Spinella et al. linked a Crohn’s disease risk allele regulating SKAP2 expression to T lymphocyte function. SKAP2 enhances cell adhesion while suppressing migration. Sustained TCR signaling triggers its proteolytic cleavage to enable migration. Overall, genetic alteration of SKAP2 levels drives T cell dysfunction and promotes autoimmune disease.