515 Integrated analysis of acne identifies a critical role for immune fibroblastic cells (IFCs) in the pathophysiology of acne and in the action of isotretinoin

To improve understanding of acne we evaluated host cell networks in the pilosebaceous unit and variables associated with C. acnes that promote skin inflammation. Single-cell RNA sequencing uncovered unsuspected activation specific dermal fibroblast subsets both human mice challenged by acnes. This transcriptional response was characterized initiation fat differentiation expression cathelicidin (Camp) fibroblasts; responses were validated immunostaining PREF1 CAMP these specialized perifollicular immune fibroblastic cells(IFCs). mRNA interactome analysis showed novel IFCs share a major inflammatory communication network myeloid cells acne. 3T3L1 fibroblasts then used as model for IFCs. Analysis protein injected bacterial strain-specific proinflammatory triggers genomic sequence, growth conditions plasmid incorporation, not only phylotype. Next, functional relevance demonstrated acnes-injected treated retinoic acid(RA). After RA treatment, epidermal lipid synthesis decreased while Camp PREF1+ significantly increased (p>0.0001), this decrease acneiform lesions (p>0.004). Skin biopsies patients isotretinoin also compared to pre-treatment. However, Camp-/- no significant despite inhibition synthesis. These observations reveal previously functions IFCs, acnes, are involved pathophysiology