Project Details
Projekt
Deciphering endogenous and environmental factors impacting on development and function of iNKT cell subsets
Applicant
Dr. Hristo Georgiev
Subject Area
Immunology
Term
from 2017 to 2020
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 395810532
Invariant natural killer T (iNKT) cells are referred as an innate-like T cell subset with the capacity for fast and robust cytokine response granting them prominent roles in diverse immune processes. Although sharing common features with conventional T cells, iNKT cells possess a limited T cell receptor repertoire recognizing glycolipid/phospholipid antigens presented by CD1d. The latest studies in the field proposed a subdivision of the iNKT cells into three (iNKT1, iNKT2 and iNKT17) subsets in accordance to their functional properties. However, the developmental interconnections between the iNKT subsets still remain vague which requires more detailed studies of the differentiation pathways of the iNKT subsets.In the recent years another group of innate immune cells termed innate lymphoid cells (ILCs) gained huge attention. Despite the lack of T cell receptor (TCR) on their surface, ILCs were shown to share astonishing resemblance at functional level with iNKT cell subsets which recently was shown to be true at transcriptional level as well. As iNKT cells, ILCs are subdivided into tree effector groups shown to be crucial in various immune responses including expulsion of helminths infection. The latter mechanism involves chemosensory activation of intestinal epithelial tuft cells propelling their proliferation and IL-25 production. This in turn leads to ILCs expansion and an IL-13/IL-4 coined response resulting in clearance from the worms. Therefore, guided by the close resemblance between iNKT and ILCs cell subsets and a recent discovery of tuft-like cells in the thymus, we hypothesize that intestinal microbiota can impact on the development of thymic iNKT cell subsets via chemosensory signalling pathways. Hence, this proposal is aiming at investigating the possible impact of local IL-25 production by thymic tuft-like cells on iNKT2 cell development and function. In addition, it is intended to elucidate a putative chemosensory signalling pathway involved in the IL-25 regulation and the corresponding influence of symbiotic microbiota on it. In parallel, this study will focus on examining the role of a couple of cytokines presumed to govern the development and the effector functions of iNKT1 and iNKT17 cell subsets. This part of the study will include experiments in steady-state conditions and in a thymus injury model.The data and the insights gathered by the proposed research project would be a further step in unravelling the elusive nature of iNKT cells developmental steps and functional networks they form.
DFG Programme
Research Fellowships
International Connection
USA
