Cytokines, Human Immunology, T-lymphocytes
What we investigate
The focus of our laboratory is the analysis of the immune response in humans to different classes of antigens, such as microbial pathogens, commensals, allergens or self-antigens, in physiological and pathological conditions to understand mechanisms of immune function and dysfunction and to translate basic findings to the medical setting.
Our research in more detail
Distinct T-cell subsets promote protective responses to different pathogens but also pathogenic responses in different tissues. We originally identified Th22 cells as a subset of skin-homing memory T-cells that are found in individuals with inflammatory skin disorders, including psoriasis. We also described distinct types of human pro-inflammatory and immunoregulatory Th17 cells responding to C. albicans or S. aureus and, more recently, Th1/17 cells broadly cross-reactive against Enterobacteriaceae, a large family of commensal and opportunistic pathogens of the intestine. Our current work aims to extend this analysis to microorganisms in the skin, with a particular focus on the
T-cell responses to commensal and pathogenic microbes in skin diseases, such as atopic dermatitis (AD) and psoriasis. We are particularly interested to follow up in humans recent observation in mice showing that S. epidermidis, a common colonizer of the human skin, can induce CD8+ T-cell responses that are restricted to the non-classical MHC class I molecule H2-M3 and recognize peptides that contain an N-formyl methionine (PMID: 29358051). Interestingly, these T-cells express a defined gene signature distinct from pathogen-specific T-cells, promote protection to pathogens and accelerate skin wound closure. Our studies investigate whether such form of immunity exists in humans and whether it is altered in pathological conditions.
SKINTEGRITY.CH Principal Investigators are underlined:
- Duhen T, Geiger R, Jarrossay D, Lanzavecchia A, and Sallusto F (2009). Interleukin 22 but not interleukin 17 production by a subset of human skin-homing memory T cells. Nat Immunol 10, 857.
- Zielinski CE, Mele F, Aschenbrenner D, Jarrossay D, Ronchi F, Gattorno M, Monticelli S, Lanzavecchia A, and Sallusto F (2012). Pathogen-induced human Th17 cells produce IFN-γ or IL-10 and are regulated by IL-1β. Nature 484, 514.
- Aschenbrenner D, Foglierini M, Jarrossay D, Hu D, Weiner HL, Kuchroo VK, Lanzavecchia A, Notarbartolo S*, and Sallusto F* (2018). An activation-induced immunoregulatory and tissue-residency program modulated by c-MAF in human memory Th17 cells. Nat Immunol 19, 1126. +Joint last authors.
- Sparber F, De Gregorio C, Steckholzer S, Ferreira FM, Dolowschiak T, Ruchti F, Kirchner FR, Mertens S, Prinz I, Joller N, Buch T, Glatz M, Sallusto F, and LeibundGut-Landmann S (2019). The skin commensal yeast Malassezia triggers a type 17 response that coordinates anti-fungal immunity and exacerbates skin inflammation. Cell Host Microbe 25, 389.
- Cassotta A*, Goldstein JD*, Durini D, Jarrossay J, Baggi Menozzi F, Venditti M, Russo A, Falcone M, Lanzavecchia A, Gagliardi MC, Latorre D+, and Sallusto F+. Broadly reactive human CD4+ T cells against Enterobacteriaceae are found in the naïve repertoire and are clonally expanded in the memory repertoire. Eur J Immunol, under revision. *Joint first authors; +Joint last authors.