TGFß activating integrins ß6 and ß8 are dysregulated in inflammatory skin disease and cutaneous melanoma.

BACKGROUND: Integrins avß6 and avß8 are expressed by keratinocytes and transactivate latent TGFß. In a murine model, integrin mediated activation of TGFß has been shown to be critical in maintaining skin homeostasis, specifically playing roles in epidermal retention of Langerhans cells and resident memory cells T cells (Trm). OBJECTIVE: We examine expression of Integrins ß6 and ß8 in human skin, inflammatory skin disease, benign nevi, and melanoma and hypothesize that integrin expression is dysregulated in disease. METHODS: Using immunohistochemistry, we stained tissue from normal human skin (n = 8), psoriasis (n = 6), atopic dermatitis (n = 6), lichen planus (n = 5), benign nevi (n = 24), and melanoma (n = 25) with anti-integrin ß6 and anti-integrin ß8 to survey expression pattern. We also performed a retrospective chart review in the melanoma cohort to examine if integrin ß6 and ß8 expression was associated with increased Breslow depth and worse prognostic staging. RESULTS: Here, we show that human keratinocytes express integrins ß6 and ß8, similar to murine keratinocytes. We also found that inflammatory skin conditions have increased Integrin ß6, but not Integrin ß8 expression. Furthermore, we identified that melanomas have greatly increased expression of integrin ß8 compared to nevi. Additionally, high expression of integrin ß8 was correlated with greater Breslow depth at diagnosis and with worse prognostic staging. CONCLUSION: These findings demonstrate that like murine keratinocytes, human keratinocytes express integrin ß6 and ß8 under steady state conditions. Moreover, altered integrin expression may participate in the development or maintenance of cutaneous inflammation as well as tumor immune evasion.

What Do You Want Us to Know?: Learning From Life Stories to Improve Veterans' Healthcare Experiences.

My Life My Story (MLMS) is a national Veterans Health Administration (VA) life story interview program that aims to provide more humanistic care for veterans by focusing on the patient as a person. Our project took place at the Pittsburgh VA Healthcare System and had 3 main goals: (1) describe themes that emerge in MLMS interviews from the prompting question, what do you want your healthcare provider to know about you?; (2) identify topics of importance to veterans and suggest ways for healthcare providers to explore them; and (3) foster a culture at the Pittsburgh VA that places not only the health but also the personal triumphs, hardships, and aspirations of veterans at the center. Veterans provided verbal consent to have their previously recorded stories used in this study. Stories were coded and then analyzed for patterns and themes. A total of 17 veterans participated in our study. Themes that emerged from the stories include (1) Early Hardships; (2) Economic Disadvantage; (3) Polaroid Snapshots; (4) Around the World; (5) Haunted by Combat; (6) Life-altering Moments; (7) Homecoming; (8) Romantic Beginnings & Obstacles; (9) Inequity across Gender & Race; and (10) Facing Mortality. This study's findings underscore the need to address the traumas associated with military service, as well as the challenges faced with re-integration into civilian life, when working with veterans. The MLMS interviews explored in this study can help clinicians identify topics of importance to veterans, strengthen their relationships with their patients, and improve the care that veterans receive.