Peyer’s Patches are secondary lymphoid organs which develop in the gastrointestinal tract during embryogenesis or in early post-natal period, and trigger adaptive immune responses to pathogens. Much of the high-level detail of PP formation is now understood. However, why such formations occur at particular locations, usually on the outside of a bend in the intestine tract, and why there is variation in size and number of PP is unclear. The behaviour of individual parts of the system has been identified experimentally, yet it is difficult to quantify the effect the each part has on the end result of the process (the formation of the patch).
To demonstrate how useful computer simulations can be in helping us understand immune system formation, we have used published and ongoing laboratory data to develop a computer simulation which replicates lymphoid organ development. We have performed experiments on the computer that have informed future lab investigations, and experiments which are not currently possible to perform in a laboratory. The simulator will be made available to all biologists, to ensure that they can use this alongside their ongoing laboratory work, and others are able to comment on the results. We have also developed and used a range of statistical tools to build confidence in simulation results, with the aim of demonstrating the potential the technique has not just in simulating the development of lymphoid organs but improving our understanding of the immune system as a whole. This work is conducted by Dr Mark Coles, Professor Jon Timmis, and Dr Kieran Alden at York, and Dr Henrique Veiga-Fernandes at the Institute of Molecular Medicine in Lisbon.
Figure 9 from our Frontiers in Immunology paper. Images of typical simulation runs at a time-point representing 72 hours of PP development. Conditions have been created which replicate known phenotypes from mice: (A) Control, (B) RET– / – LTin cells (simulated knockout), (C) Chemokine deficiency (simulated CXCL13, CCL19/21 knockout), (D) LTin-deficient mice (simulated RORγ– / –mice), (E) doubling number of LTi cells (IL-7Tg mice).
- Differential RET signaling responses orchestrate lymphoid and nervous enteric system development. A.Patel, N.Harker, L. Moreira-Santos, M.Ferreira, K.Alden, J.Timmis, K.Foster, A.Garefalaki, P.Pachnis, P.S.Andrews, H.Enomoto, J.Milbrandt, V.Pachnis, M.C.Coles, D.Kioussis, H.Veiga-Fernandes. Science Signalling
- Pairing experimentation and computational modelling to understand the role of tissue inducer cells in the development of lymphoid organs. K.Alden, J.Timmis, P.S.Andrews, H.Veiga-Fernandes, M.C.Coles. Frontiers in Immunology.