Prof. Cornelia Halin

Keywords

Intravital microscopy, Immune modulation, Lymphatic vessels, Mouse models, Tertiary lymphoid structures

What we investigate

Our laboratory studies the role of lymphatic vessels in skin inflammation and cancer. One focus lies in elucidating basic mechanisms and the significance of leukocyte migration through afferent lymphatic vessels. Moreover, we seek to identify new therapeutic targets for the treatment of disorders that involve the lymphatic vasculature.

Our research in more detail

Abbildung Werner
Screenshot from time-lapse intravital microscopy experiments performed in the inflamed ear skin of fluorescent reporter mice. (A) Red-fluorescent T cells migrating in the interstitial tissue and within green-fluorescent lymphatic capillaries. Scale bar: 100 µm. (B) Yellow-fluorescent dendritic cell interacting with a green-fluorescent T cell within a red-fluorescent lymphatic capillary. Scale bar: 50 µm.

Tissue inflammation and tumor growth are accompanied by substantial remodelling and expansion of blood and lymphatic vessels. An expanded network of functional lymphatic vessels is thought to alleviate inflammation by facilitating fluid drainage and clearance of inflammatory mediators and of leukocytes from tissues. Conversely, tumor lymphangiogenesis is associated with lymph node metastasis and poor patient prognosis. Emerging findings further indicate the contribution of tumor lymphatics to immunosuppression. Performing intravital microscopy in inflamed skin of fluorescent reporter mice we find that dendritic cells and T cells spend hours migrating and interacting with lymphatic endothelial cells (LECs) or with each other within afferent lymphatic capillaries. Moreover, our results from transcriptomics analyses of dermal LECs show that lymphatics are a rich source of immune-modulatory factors. By dissecting the role of these factors and cellular interactions we aim to further investigate the immune-modulatory function of lymphatic vessels in tumors and skin inflammation. In the context of SKINTEGRITY.CH, we also plan to investigate the interplay between lymphatics and tertiary lymphoid structures in skin cancer. While we mainly use mouse models for addressing our research questions, we also aim to validate our findings in human tissues, in collaboration with our clinical partners.

Selected publications

SKINTEGRITY.CH Principal Investigators are underlined:

  • Vranova M, Friess MC, Haghayegh Jahromi N, Collado-Diaz V, Vallone A, Hagedorn O, Jadhav M, Willrodt AH, Polomska A, Leroux JC, Proulx ST, and Halin C (2019). Opposing roles of endothelial and leukocyte-expressed IL-7Rα in the regulation of psoriasis-like skin inflammation. Sci Rep., 9, 11714.
  • Hunter MC, Teijeira A, Montecchi R, Russo E, Runge P, Kiefer F, and Halin C (2019). Dendritic cells and T cells interact within murine afferent lymphatic capillaries. Front Immunol. 10, 520, 2019.
  • Willrodt AH, Beffinger M, Vranova M, Protsyuk k D, Schuler K, Jadhav M, Heikenwalder M, van den Broek M, Borsig L, and Halin C (2017). Stromal expression of activated leukocyte cell adhesion molecule (ALCAM) promotes lung tumor growth and metastasis. Am J Pathol., 187, 2558.
  • Teijeira A+, Hunter MC+, Russo E, Proulx ST, Frei, T, Debes GF, Coles, M, Melero, I, Detmar, M, Rouzaut, A, and   Halin, C (2017). T cell migration from inflamed skin to draining lymph nodes requires intralymphatic crawling supported by ICAM-1 / LFA1 interactions. Cell Rep 18, 857. +Joint first authors.