Hila K. Novak

Abstract Targeting the JAK/STAT pathway has emerged as a key therapeutic strategy for managing Rheumatoid Arthritis (RA). JAK inhibitors suppress cytokine-mediated signaling, including the critical IL-6/STAT3 axis, thereby effectively targeting different aspects of the pathological process. However, despite their clinical efficacy, a subset of RA patients remains refractory to JAK inhibition, underscoring the need for alternative approaches.

Efficient activation of the T cell receptor (TCR) on T cells by antigen-presenting cells (APCs) requires the formation of a stable interface (the immunological synapse) between both cell types. T cell adhesion to APCs is mediated by the T cell integrin LFA-1, the activation of which depends on the small guanosine triphosphatase (GTPase) Rap1. Patients with mutations in the gene encoding Rap1 have an immunodeficiency caused by defective T cell adhesion. Azoulay-Alfaguter et al.