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Immune response induced by colorectal irradiation: therapeutic manipulation of Toll-like receptors

Jean-Victor Lacavé-Lapalun has defended his thesis on 16th May 2013 in Paris.

Document type > *Mémoire/HDR/Thesis

Keywords >

Research Unit > IRSN/DRPH/SRBE/LRTE

Authors > LACAVÉ-LAPALUN J-V.

Publication Date > 16/05/2013

Summary

Exposure of the abdomino-pelvic sphere to ionizing radiation is associated with a high
incidence of complications. Radiation therapy may cause short and / or long-term harmful
effects. In the most severe cases and in the absence of heavy treatments, the appearance of
ulcers may induce the death of patients. Clinical trials are being conduced with Mesenchymal
Stem Cells (MSC) to cure theses complications. Others studies indicate that the injection of
bacterial motifs limits the radiotoxicity in the intestine. They stimulate receptors (Toll-Like-
Receptors (TLR)) located on the surface of epithelial and intestinal immune cells. The first
aim of this doctoral work is to characterize the effects of TLR stimulation on immunity and
tissue repair using a model of localized colorectal irradiation at 20 Gy (acute effects of
radiotherapy) on a rat. The thesis then aims to potentiate the effects of the MSC treatment
when adding TLR ligands upon localized colorectal irradiation at 27 Gy (accidental
complications). This work, using a 20 Gy exposure, show that TLR stimulation improves
homeostasis (normalization of T cells, induction of regulatory T cells (Treg) and macrophages
"anti-inflammatory" M2). On the 27 Gy colorectal model, the injection of TLR ligand before
CSM transplant improves the immune climate by reducing pro-inflammatory cytokines and
inducting Treg and M2 cells. These modulations could contribute to improving the
implantation and effectiveness of CSM. The observations have all shown that the stimulation
of immunity is an approach to minimize radiation-induced lesions.

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