Inter-organ communication: The impact of IL-17 on lung immune landscape and pathophysiology following a sciatic nerve injury

Fikir Asfaw, a 31-year-old Medical Doctor currently doing her PhD in innate immunity and inflammation at Instituto Gulbenkian De Ciência, Portugal since September 2022. She was born and raised in the capital city of Ethiopia, Addis Ababa. She finished high school top of her class and joined medical school at Hawassa University in 2009. During her studies, she fell in love with the ingenuity of treating children, which led to her Pediatrics career. After her 3 years of training, in January 2020 she started working at Wachemo University Hospital; as an Assistant professor in the Pediatric department. 2 years later, Fikir moved back to the capital city as a full-time Pediatrician in a private pediatric specialty clinic until she started her PhD.
Both her mother, a drafting specialist, and father, a civil engineer, are both academic enthusiasts always supporting her scientific endeavor. Being the first daughter in her family, Fikir was raised taking most of the responsibility to her siblings and keenly close to her family which had evolved with her profession as she spent her day handling children. Fikir has lifelong friendships and close relations with her colleagues, as she considers having strong social bonds the main aspect of a healthy life.

Fikir is currently enrolled in the University of Lisbon’s Doctoral Programme of the Lisbon Academic Medical Centre – Ph.D. CAML, and participated in the local IGC’s IBB Programme.

Well, for me it has always been medicine! Becoming a physician and academician! From the early days of school, I can ever remember all I wanted was to become a Medical Doctor. Perhaps I have always admired a profession that is a dedicated reader, an enquirer, and a solver at the same time; and in my eyes, a Physician was all of those. Dedicating my life to studying the human body during its prime well-being and fallout is a great knowledge to acquire, I thought. In addition, I have always been a science person, I liked to believe what I saw and followed logical explanations to occurrences. I loved every topic I studied in Biology, especially about health and sickness. I would say I have decided to become a Physician since the time I started learning science and its implications in our lives.

For the love of science! During my residency, I used to find myself reading different journals and publications; old or new; and I remember the strong feeling of envy I got for the love and dedication each researcher showed to that piece of work. During my second year, I read this paper written about normothermia and the determination of fever; and it forever changed my perspective as a researcher. It was that day I decided that being a clinician would not suffice my academic endeavor because I have always admired a life dedicated to science. I want to be one of the experts who build bridges for scientific discoveries and human health.

My project aims to investigate the role of specific immune cell candidates and mediators in inter-tissue communication. In particular, I aim to understand how a local inflammation resulting from an injury of the sciatic nerve can spread and impact other organs. Accordingly, we have observed an accumulation of immune cells in the lung and mesenteric lymph nodes (mesLNs) from mice that underwent a sciatic nerve crush surgical procedure, an alteration exacerbated in IL-17-deficient mice compared to their littermate controls. Thus, we will characterize the lung immune landscape and pathophysiological response upon nerve injury, using a multifaceted approach integrating flow cytometry, single-cell RNA sequencing, histology, and proteomic analysis to address three main objectives. These are; (1) to characterize the immune landscape in the lung, draining LNs and other peripheral lymphoid organs, upon sciatic nerve injury; (2) to uncover the role of IL-17 and the microbiota during inter-tissue communication in this context; (3) to reveal the functional implications of this process on lung pathophysiology.

Patients suffering from peripheral neuropathies and traumatic nerve injury later develop complications like anxiety, memory impairment and dysbiosis, worsening their compromised quality of life. Chronic skin pathologies such as psoriasis and atopic dermatitis are also linked to systemic inflammation affecting multiple organs, namely the kidney, the lungs and the gut. This project will elucidate key mechanisms by which IL-17 modulates inter-organ communication, particularly focusing on the lung immune landscape following sciatic nerve injury. By contributing to a better understanding of this paradigm, these findings may have a key clinical relevance, as one of the major causes of impaired quality of life in acute or chronic inflammatory disease is the spread of pathology from the primary organ. Of note, treatments that target IL-17 have shown positive results in chronic inflammatory conditions like psoriasis, ankylosing spondylitis, and inflammatory bowel disease. Therefore, these findings are poised to advance the development of innovative immunotherapeutic strategies for treating inflammatory diseases and enhancing tissue repair. As such, being part of a team that has long-standing experience in Immunology and Neuroscience working on one of the most common and uncurable morbidities in our generation plays a huge role in my professional and medical career by building an inquisitive mind that bases research discoveries to tackle yet untreated and poorly understood illnesses.

Although I don’t succeed as much, I believe in balancing work/science and leisure. Whenever I am not at work or reading, I cherish the company of my family and friends discussing debatable topics or playing boring games. I love every minute I get to spend with my little nephews and nieces, it is happiness in its truest form. I love watching movies and listening to music, and also catching art exhibitions; classic and medieval period inspiration is my favorite in all sections. I enjoy taking long walks and playing ground tennis. I am a keen advocate of mental health and inner beauty, but I feel more emotionally devoted to the healthy upbringing of children. I strongly believe in giving back to the community; whenever I get the time and opportunity, I try to help, whether it is donating blood, organizing fundraisers for the homeless, or taking a visit to orphanage centers back in Ethiopia.