Lymphoid Development and Regulation
The immune system is composed of myeloid and lymphoid cells that collectively protect the body from bacteria, parasites, fungi, or viruses, and from the growth of tumor cells. Hematopoietic stem cells (HSCs) are ultimately responsible for the production of all cells in the immune system. Throughout a lineage commitment process, multipotent HSCs differentiate and generate progeny increasingly restricted in their lineage fate choices, to finally develop into a fully committed progenitor with single lineage potential. The development of distinct cell lineages is driven by a network of transcription factors and extra cellular signaling such as growth factors and cytokines. The lymphoid lineage includes: T, B and natural killer (NK) cells. Although different developmental stages of B and T cells have been identified, NK cell development has not been well characterized. The broad interest of our group is to characterize the cellular stages and regulatory pathways governing the development of lymphoid cells in human and in mouse. Our most recent studies specifically focus on NK cells. On the road map of NK lineage development, several questions remain and our research focuses on three developmental aspects: progenitor identity, regulation and function. The gained knowledge could lead to a better understanding of hematopoietic disorders such as immune-deficiencies, myeloproliferative disease and leukemia.
- To identify and characterize novel lymphoid progenitors and establish sequential differentiation stages from HSCs to mature NK cells
- To identify key regulatory pathways driving the transition and restriction points at these cellular stages: controlling NK cell lineage identity, development and function
- To understand how leukemic cells escape NK cell immune-surveillance and how the disease onset and progression alters NK cell development
NK cells are key components of the innate immune system that can directly recognize and eliminate infected cells, stressed cells and cancer cells without previous activation or expansion. Patients with myelodysplastic syndrome and leukemia show reductions in NK cell numbers and defects in NK cell activity. The severity of NK cell impairment is positively linked to more advanced cancer stages. NK cell –based immunotherapy has been carried out to treat leukemia, and other type of tumours, and ex vivo expanded NK cells show extensive cytotoxicity against cancer cells without affecting healthy cells. The important anti-tumor role for NK cells provided a rational for a growing number of clinical trials based on adoptive transfer of autologous and allogeneic NK cells. A better understanding of NK cell origin and regulation will move the field forward, and will not only contribute to a greater understanding of human lymphoid and NK cell development but will also pave the way for establishing a new generation of NK cell-based therapies with high target specificity. Understanding how NK cell compartment is altered during the onset and progression of leukemia will allow developing therapeutic approaches to restore NK cell activity in patients.
(name linked to profile in Lund University research portal)
PrincipaI investigator, Professor, Ewa [dot] Sitnicka_Quinn [at] med [dot] lu [dot] se
Postdoc, Gladys [dot] Telliam [at] med [dot] lu [dot] se
Postdoc, dang [dot] nghiem_vo [at] med [dot] lu [dot] se
Research Engineer, Olga [dot] Kotova [at] med [dot] lu [dot] se