Figure 1. Inflammatory process in acne pathogenesis.

Figure 1 (not at scale) illustrates how several pathogenic factors convey and promote inflammation in acne. Continuous narrow arrows represent events in acne pathogenesis, broad arrows show cell infiltration, grey dashed lines represent cell magnifications of sebocytes and keratinocytes, and black dashed lines represent yet unproven suggested pathways. Color conventions are blue for T cells, green for phagocytes (monocytes and macrophages) and innate immunity cells (neutrophils and skin resident dendritic cells). Insulin, IGF-1, abnormal lipid production and C. acnes are the main triggering factors involved in acne pathogenesis. These factors are recognized by sebocyte and keratinocyte receptors (1). Sebocytes recognize insulin and IGF-1 promoting abnormal sebum production (2). C. acnes is recognized in sebocytes and keratinocytes which produce pro-inflammatory cytokines through NF-κB and NLRP3 activation (3). Moreover, this bacterium can be recognized and endocyted by phagocytes and DCs in dermis and epidermis (4). Palmitic acid derived from C. acnes lipase activity is also recognized through through TLR2, resulting in the production of IL-1β (5). Sebum production and hyperkeratinization develop sebum plugs that favor C. acnes growth (6). Pro-inflammatory cytokine production and C. acnes outgrowth result in tissue perturbation and infiltration of the bacterium and inflammatory molecules (7). Consequently, Th cell activation and maturation occur in the dermis (8). Different Th subpopulations are related to acne pathogenesis: Th1 or Th1/Th17 stimulate phagocytes (9), Treg might not be capable of controlling iTh17 and/or Th22 that activate neutrophils and likely promote keratinocyte proliferation (10). Finally, stimulated leucocytes infiltrate through damaged tissue and promote further inflammatory reactions (11). Details in cytokine production and immune cell stimulation by acne pathogenic factors are described through the text and depicted in this figure. Abbreviations: NF-κB (Nuclear Factor kappa B), ROS (Reactive Oxygen Species), PI3 (Phosphoinositide 3-Kinase), AKT (Protein Kinase B), (MAPK) Mitogen-Activated Protein Kinase, mTORC1 (Mammalian Target of Rapamycin Complex 1), SREBP-1 (Sterol Regulatory Element-Binding Protein 1), Th (T helper cells), Treg (T Regulatory cells), iTh (Inflammatory T helper cells), TNFa (Tumor Necrosis Factor a), DC (Dendritic Cell). Figure created with Biorender.com.