1. Toll-like receptors: Applications to dermatologic disease
Sammy S.W. Kang, MD, Lynda S. Kauls, MD, Anthony A. Gaspari, MD 
Journal of the American Academy of Dermatology 
Volume 54, Issue 6, Pages (June 2006)
DOI: /j.jaad
Copyright © 2006 American Academy of Dermatology, Inc. Terms and Conditions

2. Fig 1
The Toll–interleukin 1 receptor (TIR) motif is conserved among all Toll-like receptors (TLR), interleukin 1 receptors (IL-1R), and adaptor molecules such as myeloid differentiation factor 88 (MyD88), Toll–interleukin 1 receptor domain–containing adaptor–inducing interferon-β/Toll–interleukin 1–containing adaptor molecule-1 (TRIF/TICAM-1), and Toll–interleukin 1 receptor domain–containing adaptor protein (TIRAP). Ig, Immunoglobulin; LRR, leucine-rich repeat, MAL, myeloid differentiation factor 88 adaptor-like protein.
Journal of the American Academy of Dermatology  , DOI: ( /j.jaad )
Copyright © 2006 American Academy of Dermatology, Inc. Terms and Conditions

3. Fig 2
Those pathways that are common to Toll-like receptors (TLR), as well as recently elucidated pathways that demonstrate receptor specificities, are depicted. AP-1, Activator protein-1; Elk-1, ETS domain-containing protein; ERK, extracellular-signal-regulated kinase; IFN-β, interferon-β; IFNR, interferon receptor; IκB, inhibitor of NF-κB; IKK, inhibitor of NF-κB kinase; IRAK, interleukin 1 receptor–associated kinase; IRF, interferon regulatory factor; JAK, janus kinase; JNK, c-Jun-NH2-terminal kinase; MD2, TLR4-associated molecule; MKKs, MAPK (mitogen-activated protein kinase) kinases; MyD88, myeloid differentiation factor 88; NF-κB, nuclear factor-κB; P, phosphate group; p38, a MAPK; STATs, Signal Transducer and Activator of Transcription proteins; TAK-1, transforming growth factor b-activated kinase-1; TBK1, TANK-binding kinase-1; TIRAP, Toll–interleukin 1 receptor domain–containing adaptor protein; Tollip, Toll-interacting protein; TRAF-6, tumor necrosis factor receptor–associated factor 6; TRIF/TICAM-1, Toll–interleukin receptor domain–containing adaptor–inducing interferon-β/Toll–interleukin 1–containing adaptor molecule-1.
Journal of the American Academy of Dermatology  , DOI: ( /j.jaad )
Copyright © 2006 American Academy of Dermatology, Inc. Terms and Conditions

4. Fig 3
Alternate cytokine production profiles can be produced after stimulation of identical Toll-like receptors due to the alternate downstream signaling mediated by TRIF. A, Excess TNF receptor–associated factor 6 (TRAF-6) blocks the binding of TANK-binding kinase-1 (TBK-1) leading to an increased production of NF-κB, whereas (B) production of IFN-β is produced if TNF receptor–associated factor 6 binding is disrupted. This illustrates the myriad of cellular responses elucidated by a limited repertoire of receptors. IRF-3, interferon regulatory factor 3.
Journal of the American Academy of Dermatology  , DOI: ( /j.jaad )
Copyright © 2006 American Academy of Dermatology, Inc. Terms and Conditions

5. Fig 4
Photoimmunosuppression. UV radiation can up-regulate endogenous Toll-like receptor (TLR) ligands such as HSPs (1, 2). By ligating Toll-like receptors, these stress signals activate the Toll–IL-1 receptor signaling cascade (3, 4), leading to the production of immunosuppressive IL-10 and TNF-α (5). The immunosuppressive cytokine milieu is further supported by the production of IL-10 by regulatory T cells (Treg). KC, keratinocyte; LC, Langerhans cell; LN, lymph node.
Journal of the American Academy of Dermatology  , DOI: ( /j.jaad )
Copyright © 2006 American Academy of Dermatology, Inc. Terms and Conditions

6. Fig 5
Toll-like receptor (TLR) signaling defect in xeroderma pigmentosum. Defective Toll-like receptor 3 signaling may be linked to the vulnerability of XP patients to UV-induced skin cancers. As stress signals cannot properly activate Toll–IL-1 receptor pathways to produce IL-12 (an important antagonist of IL-10), the effects of immunosuppressive cytokines would predominate. Also, the tumoricidal activity of NK cells is likely compromised. APC, antigen-presenting cell; KC, keratinocyte; Treg, regulatory T cell.
Journal of the American Academy of Dermatology  , DOI: ( /j.jaad )
Copyright © 2006 American Academy of Dermatology, Inc. Terms and Conditions

7. Fig 6
Inherited IL-1 receptor–associated kinase (IRAK)-4 deficiency. Mutations of the Irak4 gene result in a truncated form of the protein, which prevents the proper assembly of the Toll receptor complex and activation of crucial signaling molecules. Degradation of inhibitor of NF-κB (IκB) does not occur, and as a result, NF-κB cannot translocate into the nucleus to initiate the transcription of proinflammatory cytokines. IKK, inhibitor of NF-κB kinase; P, phosphate group; Staph, staphylococcus; Strep, streptococcus; TAK-1, transforming growth factor β-activated kinase-1.
Journal of the American Academy of Dermatology  , DOI: ( /j.jaad )
Copyright © 2006 American Academy of Dermatology, Inc. Terms and Conditions

8. Fig 7
Toll-like receptor 4 (TLR4) mediates the deleterious effects of lipopolysaccharide (LPS). The C57BL/10ScCr mouse has a chromosomal deletion of the Lps locus and hence completely lacks Toll-like receptor 4 expression. In this animal model that utilizes the C57BL/10ScCr and other transgenic mouse strains expressing increasing amounts of Toll-like receptor 4, the level of Toll-like receptor 4 expression was shown to dictate the animal's response and susceptibility to LPS.
Journal of the American Academy of Dermatology  , DOI: ( /j.jaad )
Copyright © 2006 American Academy of Dermatology, Inc. Terms and Conditions