516 Possible role of ILC1 in the pathogenesis of alopecia areata (AA)

Abstract

For the last several decades, there are numbers of research done to reveal the importance of gut microbiome regarding human health and disease. One of the typical inflammatory skin disease is atopic dermatitis. The role of gut microbiome is becoming known in atopic dermatitis and the bacteria to cause the disease and probiotics to prevent the disease is being researched. We analyzed the gut microbiota of the inflammatory skin model mouse named ICE (keratin 14-specific Interleukin-1 converting enzyme overexpressing transgenic mouse). ICE had an elevatedcolonization of Staphylococcus genus and Streptococcus genus compare to those of wild type. When the ICE was treated with anti TNF-a antibody, the percentage of these bacteria had significantly decreased (p ¼ 0.018, p ¼ 0.031, respectively). We are going to present in this poster about the differences of skin reaction and cytokine production by orally administrating of isolated bacteria into sterilized wild type mice and causing skin inflammation. Our skin is daily aggressed by environmental factors and by certain personal care products (cleansers, deodorants, etc).Our obsession with cleanliness may do more harm than good for the balance of our skin's microbiota and skin health. It has been observed that overcleanliness leads to an impairment of the skin barrier function and of skin microbiome balance leading to increased sensitivity, irritation and dryness. We explored the effect of a common surfactant found in hygiene products, on the physical skin and microbiotic barrier in vivo. At first, we applied SLS (Sodium Lauryl Sulfate, 0.5% occlusive patch for 24h) and we explored its effect on the skin microbiota using metagenomic sequencing (16S rDNA) before and 1 day after SLS application. Secondly, we explored skin microbiota and skin barrier function evolution over 7 days after a 1% SLS challenge in the presence of a formula containing purified rapeseed phytosterols and one containing its vehicle. Skin barrier function was assessed before, after SLS and 7 days after applying phytosterols and vehicle by measuring TEWL. Finally, skin microbiota recovery after a 0.5% SLS patch in presence of the same formula containing phytosterols was assessed at the same timepoint; (16S metasequencing). We confirmed that the surfactant impaired skin barrier function and evidenced that it decreased the commensal bacteria while increasing the opportunistic pathogenic bacteria. At the phylum level actinobacteria were decreased by 14% and at the family level, corynebacteriaceae, micrococcaceae and propionibacteriacea were decreased (-42%, -34%, -11%). At the genus level corynebacterium, micrococcus, paracoccus and propionibacterium were decreased (-42%, -39%, -36%, -11%), whereas pseudomonas and pantoea were increased (x2, x117). Interesting results were also obtained on staphylococcus (+38%), but a more resolutive technic is necessary to discriminate between strains. To counterbalance these SLS induced-modifications, we evidenced that purified phytosterols provide benefits to restore sk...

Frontiers in alopecia areata pathobiology research

“…Instead, subsets of natural killer (NK) and so-called ''unconventional'' T cells (invariant natural killer T [iNKT] cells, gd T cells, classic NK cells, and type 1 innate lymphoid cells), all of which can produce large amounts of IFN-g, might also drive AA pathobiology independent of classical, autoantigen-dependent CD8 1 T-cell functions. 3,[8][9][10] Another important new frontier is the role of regulatory lymphocyte subsets, such as regulatory T (Treg) cells, gd Treg cells, NKT10 cells, and perifollicular masT cells, in maintaining the physiologic HF immune privilege (IP); the extent to which these functions are defective in patients with AA; and how this IP-protective role could be restored therapeutically in patients with established AA. 2,8,11,12 Recently, we delineated why AA does not necessarily represent a classical, autoantigen-dependent autoimmune disease in all patients with the AA hair loss phenotype and is best viewed as a stereotypical response pattern of anagen HFs to IFN-g-mediated immunologic damage, which induces a collapse of the HF's physiologic IP (Fig 1, A).…”

Mouse Models of Alopecia Areata: C3H/HeJ Mice Versus the Humanized AA Mouse Model

“…By using the humanized AA mouse model, it has been elucidated that AA pathogenesis in human skin is also affected by unconventional T cell subtypes such as NKT, iNKT10, ILC1, g/d-T, and g/d-regulatory T cells, whose numbers are significantly increased in AA compared with healthy human skin (Ghraieb et al, 2018;Kaufman et al, 2010;Laufer Britva et al, 2019), whose likely role in AA pathobiology had previously escaped murine AA research.…”

“…Because the experiments demonstrated that nonconventional T cells might play a role in human AA (Ghraieb et al, 2018;Laufer Britva et al, 2019), they suggest that targeting these immunocytes offers new opportunities for innovative therapeutic intervention. The humanized mouse model has been used to discover human-specific pharmacologic targets such as the potassium channel Kv1.3 (Gilhar et al, 2013).…”