Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: Associations, Outcomes, and Pathobiology—Thirty Years of Progress but Still Much to Be Done  Robert S. Stern, Sherrie J. Divito  Journal of Investigative Dermatology  Volume 137, Issue 5, Pages 1004-1008 (May 2017) DOI: 10.1016/j.jid.2017.01.003 Copyright © 2017 The Authors Terms and Conditions

Figure 1 IL-15 presentation and receptor binding. IL-15 is presented most effectively in trans, meaning complexed to membrane-bound IL-15Rα. This membrane-bound complex on the surface of an IL-15-producing cell binds to IL-15R homodimer, consisting of IL-15Rβ and γc subunits expressed on the surface of CD8+ T cells or NK cells. Alternatively, soluble IL-15 complexed to soluble IL-15Rα can bind to the same receptor homodimer, or soluble IL-15 can bind the heterotrimeric receptor, consisting of IL-15Rα, IL-15Rβ, and γc subunits expressed on the surfaces of CD8+ T cells or NK cells. Binding of IL-15 to its receptor induces signaling via the γc subunit to Janus kinase (JAK) 3, which, in turn, stimulates STAT 5, and the IL-15Rβ subunit to JAK 1, which, in turn, stimulates STAT 3. NK, natural killer; STAT, signal transducer and activator of transcription. Journal of Investigative Dermatology 2017 137, 1004-1008DOI: (10.1016/j.jid.2017.01.003) Copyright © 2017 The Authors Terms and Conditions

Figure 2 Pleiotropic effects of IL-15 on immune cells thought critical to SJS/TEN pathogenesis. IL-15 induces activation of skin antigen presenting cells, including macrophages (MΦ) and DC. Activation enhances both the production of proinflammatory cytokines and antigen presentation. IL-15 promotes development, expansion, and maintenance/survival of CD8+ T cells and NK cells. It also stimulates CD8+ T-cell and NK-cell activation, resulting in increased cytotoxicity and cytokine/chemokine production. IL-15 plays a role in NKT-cell expansion and homeostasis although its effects on NKT-cell activation are still under investigation. DC, dendritic cells; NK, natural killer cells; NKT, natural killer T cells; SJS, Stevens-Johnson syndrome; TEN, toxic epidermal necrolysis. Journal of Investigative Dermatology 2017 137, 1004-1008DOI: (10.1016/j.jid.2017.01.003) Copyright © 2017 The Authors Terms and Conditions