Increased presence and function of regulatory T cells may protect Nkx2.3-/- mice from DSS-induced colitis Orvos- és Egészségtudományi

34 OTDK, Orvos- és Egészségtudományi Szekció, Elméleti orvostudományok - Kísérletes immunológia, mikrobiológia I. Tagozat.

Increased presence and function of regulatory T cells may protect Nkx2.3-/- mice from DSS-induced colitis

Hallgató: Tareq Abu Dakah
Szak: általános orvos / Allgemeine Humanmedizin, Képzés típusa: o, Intézmény: Pécsi Tudományegyetem, Kar: Általános Orvostudományi Kar

Témavazetők: Zoltán Kellermayer - rezidens orvos, Pécsi Tudományegyetem Általános Orvostudományi Kar ,
Péter Balogh - egyetemi tanár, Pécsi Tudományegyetem Általános Orvostudományi Kar

Introduction: Nkx2.3 transcription factor acts as a susceptibility factor for human inflammatory bowel diseases. Mice deficient for Nkx2.3 lack endothelial MAdCAM-1, the main addressin directing lymphocytes to the mucosa. Regulatory T cells (Tregs) play an important role in intestinal homeostasis. In this work I investigated Treg frequencies and function in dextran sodium sulfate (DSS)-induced colitis in the absence of Nkx2.3.

Methods: Adult BALB/c, Nkx2.3^-/-, C57BL/6 and MAdCAM-1^-/- were used. To induce colitis mice received 2.5% DSS in drinking water for 7 days. Weights were measured daily. Tregs were isolated from colons and measured with flow cytometry. RNA was isolated from colonic samples and qPCR was performed to measure anti-inflammatory IL-10 and TGFβ mRNA levels at various time points.

Reszkts: Nkx2.3^-/- mice lost less weight and showed milder signs of colitis compared to controls, while MAdCAM-1^-/- mice developed more severe colitis. Colonic Tregs were significantly increased at day 7 in the absence of Nkx2.3 compared to BALB/c mice. mRNA for IL-10 was significantly higher at D0 and D7 in Nkx2.3^-/- mice, while TGFβ was lower at D0 compared to BALB/c mice. I also found higher Treg numbers in MAdCAM-1^-/- mice at D7; however this was not coupled with an increase in mRNA for IL-10 or TGFβ.

Conclusion: My results indicate that in Nkx2.3^-/- mice the increased presence and function of colonic Tregs may protect mice from colitis. This protection is independent of MAdCAM-1, as MAdCAM-1^-/- mice showed severe signs of colitis, and may be due to an altered stromal microenvironment in mice lacking Nkx2.3.