Molecular mechanisms of disease remission
The main objective of this study was to reveal potential endogenous homeostatic or anti-inflammatory pathways that could be harnessed for the benefit of sustained remission. To address our objective we based on a previous transcriptional analysis performed by our group. This study showed that despite complete healing of mucosal lesions, about half of those genes de-regulated during colonic inflammation remain altered in the involved remitting mucosa of UC patients (Planell, 2013).
We further exploited the transcriptional signature of UC remission and determined that the interleukin-1 receptor type 2 gene (IL1R2), a decoy receptor for the pleiotropic cytokine IL-1 (IL-1α and IL-1β), was significantly up-regulated in the mucosa during remission of the disease compared to controls and active inflammation.
Based on these observations, we hypothesize that IL-1R2 represents an endogenous locally acting molecule that may counterbalance low persistent or locally arising IL-1β production in chronic UC patients.
Graphical representation of IL-1 production and signaling. IL-1β: interleukin-1β; IL-1R2: IL-1 receptor type 2; IL-1R1: IL-1 receptor type 1; IL-1RAcP: IL-1 receptor accessory protein; TIR: Toll/interleukin-1 receptor domain; MyD88: myeloid differentiation primary response 88; IRAK 4: interleukin-1 receptor-associated kinase 4; TRAF6: tumor necrosis factor receptor-associated factor 6; ATP: Adenosine triphosphate; P2X7R: purinergic receptor P2X; NLRP3: NLR family, pyrin domain containing 3; ASC: Apoptosis-associated speck-like protein containing a carboxy-terminal CARD; NF-κB: nuclear factor kappa B; Ca: calcium; K: potassium (drawing by Rut Mora, PhD).
Transcriptional analysis of the intestinal mucosa of patients with ulcerative colitis in remission reveals lasting epithelial cell alterations.
Planell N, Lozano JJ, Mora-Buch R, Masamunt MC, Mireya J, Ordás I, Esteller M, Ricart E, Piqué JM, Panés J, Salas A.
Gut 62(7): 967-76; 2013
doi: 10.1136/gutjnl-2012-303333. Epub 2012 Nov 7. / PMID: 23135761
Commentary: “Looking beyond histological healing in ulcerative colitis: towards the establishment of a molecular signature for quiescent but progressive disease”
Chamaillard M, Chevaux JB, Peyrin-Biroulet L.
Gut 62(12):1714-23:1714-23; 2013
This manuscript is recommended by The Faculty of 1000 (http://f1000.com/717847861)
Epithelial IL-1R2 acts as a homeostatic regulator during remission of ulcerative colitis.
Mora-Buch R, Dotti I, Planell N, Calderón-Gómez E, Jung P, Masamunt MC, Llach J, Ricart E, Batlle E, Panés J, Salas A.
Mucosal Immunol 2015 (in press)