1. The Multitasking Organ: Recent Insights into Skin Immune Function
Paola Di Meglio, Gayathri K. Perera, Frank O. Nestle 
Immunity 
Volume 35, Issue 6, Pages (December 2011)
DOI: /j.immuni
Copyright © 2011 Elsevier Inc. Terms and Conditions

2. Figure 1
Tissue-Resident Memory T Cells Provide Long-Term Peripheral Immunity in Human Skin
After first skin infection (left) with a pathogen, dermal dendritic cells (DDCs) take up foreign antigens (Ags) and present them to naive T cells in the skin-draining lymph node, initiating an adaptive immune response. Ag-specific central memory T (Tcm) cells, expressing CCR7 and CD62L and mainly residing in lymph nodes, and effector memory T (Tem) cells, expressing cutaneous leukocyte antigen (CLA), CCR4, and CCR10, are generated. Tem cells migrate to sites of skin infection and remain there after the pathogen has been cleared to become tissue-resident memory T (Trm) cells. Upon second encounter with the same Ag (right), DDCs present Ag in situ to skin Trm cells, allowing a quick response to local reinfection. Moreover, DDCs present Ag to Tcm cells in skin-draining lymph nodes, giving rise to another population of Tem cells that migrate into skin and contribute to clearance of infection.
Immunity  , DOI: ( /j.immuni )
Copyright © 2011 Elsevier Inc. Terms and Conditions

3. Figure 2 Immunopathogenesis of Psoriasis
The combination of environmental factors with psoriasis-susceptibility genes triggers an orchestrated cascade of pathogenic events leading to disease initiation and plaque formation. In the initiation phase, proinflammatory crosstalk between injured or stressed keratinocytes (KCs), releasing self-nucleic acids and LL-37, recruited plasmacytoid dendritic cells (pDCs) producing IFN-α, activated dermal DCs (DDCs), and inflammatory DDCs (iDDCs), the latter producing IL-23, TNF, and nitric oxide radicals (NO·), promoting the activation of skin-resident and newly recruited T cells that lead to plaque formation. IL-23 stimulates T helper 17 (Th17) and T cytotoxic 17 (Tc17) cells, expressing cutaneous leukocyte antigen (CLA), CCR6, and CCR4, plus very late antigen-1 (VLA-1) in the epidermis, to release IL-17A, IL-17F, IL-22, and IFN-γ. IFN-γ further activates DDCs. IL-17A and IL-17F acts on KCs promoting production of T cells and neutrophil-attracting chemokines (CXCL1,3,8-11;CCL17-20) and antimicrobial peptides (AMPs): S100 proteins and LL-37. CCL20 favors the recruitment of more Th17 cells. IL-22, also produced by Th1 cells, expressing CXCR3 and skin-homing marker CLA, and Th22 and Tc22 cells, expressing CCR6, CCR10, and CLA, induces epidermal hyperplasia by impairing KC terminal differentiation. Recruited unconventional Vγ9Vδ2 T cells, expressing CLA and CCR6, are activated by pDCs-derived IFN-α and release further proinflammatory cytokines (IL-17A, IFN-γ, TNF) as well as neutrophils (Neut) and Th1 cell-attracting chemokines (CCL3-5). Infiltrating Neut, mast cells, and macrophages (M) contribute to the proinflammatory environment producing cytokines (IL-17A, TNF), AMPs (S100 proteins, LL-37), and chemokines. Crosstalk between keratinocytes producing IL-1, TNF and transforming growth factor beta (TGF-β), and fibroblasts, which in turn release keratinocyte growth factor (KGF), epidermal growth factor (EGF), and TGF-β, and possibly Th22 cells releasing fibroblast growth factor (FGFs), contribute to tissue reorganization.
Immunity  , DOI: ( /j.immuni )
Copyright © 2011 Elsevier Inc. Terms and Conditions

4. Figure 3 A Psoriasis Interactome
Gene expression data pooled from large patient samples can be used to generate a disease interactome. An interactome is a network of interconnected genes based on similar expression profiles across tissues. Differentially expressed genes between normal and psoriatic skin are shown as a heatmap. A coexpression interactome is created where nodes reflect genes and edges the degree of coexpression. This psoriatic interactome can be used as a disease-relevant molecular reference data set, against which differentially expressed gene transcripts generated from experimental models are assessed.
Immunity  , DOI: ( /j.immuni )
Copyright © 2011 Elsevier Inc. Terms and Conditions