Absence of Endothelial MAdCAM-1 in Nkx2.3-/- Mice Leads to Accumulation of Solitary Intestinal Lymphoid Tissue With Immature Phenotype.

We have recently reported that in the absence of endothelial MAdCAM-1 expression lymphocytes home to Peyer's patches of Nkx2.3^-/-mice via PNAd. However, the effect of this addressin switch on the components of solitary intestinal lymphoid tissues (SILT) has not been characterized yet. In this work we investigated the effect of Nkx2.3 absence on the distribution and DSS-induced colitis on the SILT spectrum.

BALB/c and Nkx2.3^-/-mice received DSS in drinking water for 7 days (acute) or 3 cycles (chronic). SILT structure maturity was analyzed by immunofluorescence assessed by C-kit, B220, CD45, CR1.2, and peanut agglutinin. Vasculature was characterized by endothelial addressin labeling.

In Nkx2.3^-/- colons we observed structurally normal cryptopatches and isolated lymphoid follicles. However, the number of mature components was less compared to BALB/c mice. Isolated lymphoid follicles in mutant colons were characterized by a smaller degree of vascularization compared to wild type. Endothelial cells lacked MAdCAM-1 but expressed PNAd. DSS treatment increased the ratio of mature SILT structures harboring germinal centers in BALB/c mice but had only minor effects in Nkx2.3^-/-colons.

Our results indicate the important role of MAdCAM-1 in the transformation of immature cryptopatches to mature isolated lymphoid follicles. In the absence of Nkx2.3 the appearance of PNAd does not provide complete functional compensation for the lack of MAdCAM-1.

Supported by OTKA grant K108429 and Apáczai Csere János Fellowship