Research

Identification of the transcriptional network promoting innate lymphoid cell (ILC) differentiation and controlling intestinal tissue homeostasis and mesenteric lymph node formation

Prinicipal Investigator

Scientific interest within the context of the graduate college:

Chronic inflammatory disorders are triggered and maintained by effector mediators produced by the adaptive immune system, such as T cell and B cells. In T cells, inflammatory programs are induced by the T cell receptor (TCR) in conjunction with distinct cytokines and/or environmental signals. Recently, it appeared evident that emerging innate cell subsets lacking the TCR and collectively known as innate lymphoid cells (ILCs), exhibit a similar heterogeneity of effector modules. ILCs are not only activated in the course of inflammation but colonize different organs already during embryonic development and contribute to tissue homeostasis. The signals, developmental pathways and innate receptors instructing the different effector programs and their execution in ILCs remain largely unknown. Therefore, our main research focus is devoted to study the transcriptional networks and the innate modules employed by ILCs to modulate tissue homeostasis and initiate inflammation.

Project description:

RORgt+ ILCs play a crucial role in driving fetal formation of lymph nodes and in promoting intestinal barrier homeostasis1. In our previous work, we have identified human ILC progenitors in tissues and described a transcriptional network contributing to promote lymphoid organ formation and intestinal homeostasis besides RORgt2-3. Using a combination of single cell sequencing techniques, in vitro cultures and in vivo analysis already established in the group, this project aims to define in detail the molecular dynamics underlying this transcriptional network governing ILC differentiation in the human and murine intestine.

Application details

References

  1. Juelke K, Romagnani C. Differentiation of human innate lymphoid cells (ILCs). Curr Opin Immunol. 2016; 38:75-85. doi: 10.1016/j.coi.2015.11.005.
  2. Montaldo E, Teixeira-Alves LG, Glatzer T, […], Moretta L, Mingari MC, Romagnani C. Human RORγt(+)CD34(+) cells are lineage-specified progenitors of group 3 RORγt(+) innate lymphoid cells. Immunity. 2014; 41:988-1000. doi: 10.1016/j.immuni.2014.11.010.
  3. Stehle et al, under revision