PhD Scientific Days 2026

Poster Session 3.J - Theoretical and Translational Medicine

Knock-out of PARP2 in T cells lead to spontaneous colitis with distinct segmental characteristics in PARP1 deficient mice

Name of the presenter

Ke, Haoran

Institute/workplace of the presenter

Department of Physiology, Semmelweis University

Authors

Haoran Ke¹, Dongwoog Kim¹, Máté Bencsics¹, Bálint Bányai¹, Roland Csépányi-Kömi¹, Péter Sasvári¹, Françoise Dantzer², Najat Hanini², José Yélamos³, Anna-Mária Tőkés⁴, Korsós-Novák Ágnes⁵, Rita Benkő¹, Eszter M. Horváth¹
1: Department of Physiology, Semmelweis University
2: UMR7242, Biotechnology and Cell Signaling, CNRS/Université de Strasbourg, Strasbourg, France
3: Hospital del Mar Research Institute, Barcelona, Spain
4: Department of Pathology, Forensic and Insurance Medicine, Semmelweis University
5: Department of Pathology, Toldy Ferenc Hospital and Outpatient Clinic of Cegléd

Text of the abstract

Activation of poly ADP-ribose polymerase like PARP1 or PARP2 was reported pro-inflammatory in various pathologies, including inflammatory bowel diseases. PARP1 suppression successfully dampen the inflammation in experimental colitis. Previously our group reported that conditional knock-out of PARP2 in T cells also exerted protection against LPS-induced colitis. Despite the preclinical findings, lower PARP activity in mononuclear cells and autoantibodies against PARPs were identified in IBD patients. To investigate the potential role of PARPs in intestinal inflammation, mice with a global PARP1 deletion and a T cell-specific PARP2 knock-out (DKO mice) was generated, which resulted in the development of spontaneous colitis with distinct segmental features. Histological alterations and altered TNFα levels in the large intestines suggested the colitis in DKO mice. Increased infiltration of immune cells, particularly neutrophils and T helper 1 cells was displayed in the intestinal mucosa of DKO mice, along with elevated levels of oxidative-nitrative markers like 3-nitrotyrosine and nitric oxide producing enzyme iNOS. Higher level of 4-hydroxynonenal as well as increased expression and activation of MAPK cascade members (p38 MAPK, p42/44 ERK), which mediate inflammatory signal transduction, was found exclusively in the proximal large intestines of DKO mice, suggesting a locally higher inflammatory activity, while in the distal segment DKO mice had noticeably elongated crypts, which may be resulted from the higher ratio of dividing cells (Ki-67+) at the base of the crypts. Both IL-17A level and occludin expression were suppressed in the proximal large intestines of DKO mice, which may be partially attributable to the segmental distinction, considering their roles in maintaining intestinal defense against microbiome. Our results suggested that PARPs may have certain essential roles maintaining intestinal integrity which are closely associated with lymphatic tissues. The combined genetic modification could potentially lead to harmful alterations of the mucosa and the lymphatic tissue which predisposed the spontaneous inflammation with segmental features.
This work was supported by the Hungarian National Research, Development and Innovation Office NKFIH-FK129206 (EH), NKFIH-FK128376 (RC-K), TKP2021-EGA-24 (RC-K) and Semmelweis University (EH:STIA-18).