Significance: Macrophages are invariably present and tightly regulate all phases of adult wound healing, including inflammation, granulation tissue formation, and matrix deposition with the unavoidable outcome of scar formation. In response to environmental cues, macrophages mount a “classical” pro-inflammatory M1 activation as opposed to the “alternative” M2 phenotype, with wound macrophages having long been viewed as M2 macrophages. Recent Advances: Recent studies rather point to large temporal and phenotypic variations of wound macrophages subsets. Therefore, a functional classification of macrophages according to wound-healing phases appears to better meet the in vivo complexity. In an ideal but simplistic scenario grossly reflecting normal wound healing, initial tissue injury induces inflammatory M1-like macrophages, which, upon engulfment of apoptotic neutrophils or in response to other inflammation dampening stimuli, switch toward anti-inflammatory M2-like macrophages and further toward growth factor-producing pro-fibrotic M2a-like macrophages. Although not yet documented for skin wounds, a subset of metalloproteinase-producing fibrolytic M2c-like macrophages may contribute to fibrosis resolution. Recent work identified a diversity of novel macrophage phenotypes associated with normal and pathologic wound healing, most of them ranging out of the M1/M2 paradigm. Iron-overloaded M1-like macrophages represent such a novel phenotypic subset driving the non-healing state of chronic venous leg ulcers. Critical Issues: Despite growing evidence that macrophage dysfunctions are, at least in part, responsible for pathologic wound healing, including nonhealing wounds and excessive scar formation, these are hardly specifically addressed even by modern therapeutic strategies. Future Directions: If characterized in sufficient detail, distinct macrophage subsets and their impaired functions provide ideal targets for improving wound healing.

Severe angiopathy is a major driver for diabetes-associated secondary complications. Knowledge on the underlying mechanisms essential for advanced therapies to attenuate these pathologies is limited. Injection of ABCB5⁺ stromal precursors at the edge of nonhealing diabetic wounds in a murine db/db model, closely mirroring human type 2 diabetes, profoundly accelerates wound closure. Strikingly, enhanced angiogenesis was substantially enforced by the release of the ribonuclease angiogenin from ABCB5⁺ stromal precursors. This compensates for the profoundly reduced angiogenin expression in nontreated murine chronic diabetic wounds. Silencing of angiogenin in ABCB5⁺ stromal precursors before injection significantly reduced angiogenesis and delayed wound closure in diabetic db/db mice, implying an unprecedented key role for angiogenin in tissue regeneration in diabetes. These data hold significant promise for further refining stromal precursors-based therapies of nonhealing diabetic foot ulcers and other pathologies with impaired angiogenesis.

Psoriasis is a complex genetic disease of unresolved pathogenesis with both heritable and environmental factors contributing to onset and severity. In addition to a disfiguring skin inflammation, approximately 10–40% of psoriasis patients suffer from destructive joint involvement. Previously, we reported that the CD18 hypomorphic PL/J mouse carrying a mutation resulting in reduced expression of the common chain of β2 integrins (CD11/CD18) spontaneously develops a skin disease that closely resembles human psoriasis. In contrast, the same mutation on C57BL/6J background did not demonstrate this phenotype. By a genome-wide linkage analysis, two major loci were identified as contributing to the development of psoriasiform dermatitis under the condition of low CD18 expression. Using a congenic approach, we now demonstrate that the introduction of a 9-centimorgan fragment of chromosome 10 derived from the PL/J strain into the disease-resistant CD18 hypomorphic C57BL/6J was promoting the development of psoriasiform skin disease and notably also arthritis. We therefore designated this locus psoriasiform skin disease-associated locus 1 (PSD1). High numbers of CD4+ T cells and TNF-α producing macrophages were detected both in inflamed skin and joints in these congenic mice, with a complete resolution upon TNF-α inhibitor therapy or depletion of CD4+ T cells. For the first time, we have identified a distinct genetic element that contributes to the T cell-dependent development of both psoriasiform skin disease and associated arthritis. This congenic model will be suitable to further investigations of genetic and molecular pathways that cause psoriasiform dermatitis and arthritis, and it may also be relevant for other autoimmune diseases.

Psoriasis is one of the most common dermatoses with a heterogeneous pathogenesis which can be successfully exploited therapeutically as it is increasingly well understood. Topical therapy is the gold standard for psoriasis patients with mild disease courses and for complementary and maintenance treatment in moderate and severe forms. However, while new systemic therapies are rapidly implemented in the daily routine as our pathomechanistic understanding of psoriasis evolves, the development of topical psoriasis therapies stagnates. Modern topical treatments though would require not only new active substances but also improved galenics. Due to their unique ability to directly exert biological functions, but also to deliver drugs in optimal concentrations, enabling increased therapeutic efficacy, reduced adverse effects and improved patient compliance, nanoparticles may represent ideal drug carriers for local therapeutics in psoriasis. In recent years, a series of reports added important insights into the biology of skin‐nanoparticles interactions and on how they impact the epidermal and dermal inflammatory compartments in vitro and in psoriasis plaques. Furthermore, by targeting anti‐inflammatory substances to specific skin compartments, nanotechnological advances offer the exciting opportunity to fine‐tune skin inflammation at molecular and cellular levels, paving the road to a high‐precision, skin‐directed topical therapy in psoriasis. However, nanoparticle‐based therapies have not yet found their way into clinical routine in dermatology. We here resume the current advances in the research of nanoparticles and skin inflammation in general and psoriasis in particular and discuss how this promising technology should develop in order to fulfil the requirements of an optimal skin therapy.