Immunometabolism in osteoarthritis

Jong, A.J. de (2018)

Doctoral Thesis

Immunometabolism focusses on the interplay between immunological and metabolic processes, both at a systemic and a cellular level. This thesis is divided into two parts based on these two levels. The first part focusses on the infrapatellar fat pad (IFP), an adipose tissue located in the knee, and the potential role in the pathophysiology of osteoarthritis. Therefore, we characterized the IFP based on a cellular and molecular level and found that the inflammatory state of the joint does affect the cellular load of the IFP, however, the secretory profile of the IFP does not seem to be affected. Furthermore, obesity-related changes normally found in adipose tissue were not present in the IFP. When characterizing the IFP we found two interesting cell populations, IL-6-secreting T cells and macrophages with an anti-inflammatory phenotype secreting pro-inflammatory cytokines. Both populations could be involved in the pathophysiology of the osteoarthritic joint. Furthermore, in the second part we focussed on cellular metabolism where we determined the mechanism by which fatty acids exert their effect on T cells. We found that fatty acids are not served as energy, however, whether it is used for daughter cells or influencing cell signalling remains to be elucidated.

• Immunometabolism
• Adipose tissue
• Osteoarthritis
• Inflammation
• Obesity
• Fatty acids

• All authors: Jong, A.J. de
• Supervisor: Toes, R.E.M.; Kloppenburg, G.
• Co-supervisor: Ioan-Facsinay, A.
• Committee: Huizinga, T.W.J.; Willems van Dijk, J.A.P.; Meulenbelt, I.; Bastiaansen-Jenniskens, Y.M.; Roon, J. van
• Qualification: Doctor (dr.)
• Awarding Institution: Medicine / Leiden University Medical Center (LUMC), Leiden University
• Date: 2018-02-20
• ISBN (print): 9789463323048