Deletion of the Plau gene in mice affects the frenquency of Foxp3+ cells in the

6.2 Functional analyses of one candidate gene in human Tregs and in knockout mice

6.2.4 Deletion of the Plau gene in mice affects the frenquency of Foxp3+ cells in the

Since knockdown experiments and functional assay suggested that the PLAU gene in human Tregs may play an important role in Treg function, we studied Plau-deficient knockout mice (Carmeliet et al., 1994). Plau knockout (KO) mice had similar body weights at birth compared to wild type mice. However, at the age of 22 to 26 weeks, 5% of homozygote KO mice developed rectal prolapse of a non-infectious origin and severe non-healing ulcerations at the ears around the ear tag and the face (Carmeliet et al., 1994). Upon infection with C. neoformans, Plau mutant mice showed an impaired T cell proliferation in regional lymph nodes and failed to produce high levels of Th1 cytokines (IFN-gamma and IL-12) in the lung. Instead, they exhibited increased levels of IL-5, a Th2 cytokine (Gyetko et al., 2002). However, no studies were performed so far to investigate CD4+CD25+Foxp3+ Tregs in Plau KO mice.

Here, I first examined the frequency of Foxp3+CD4+ Treg cells in different lymphatic organs, including mesenteric lymph nodes (mLN), peripheral lymph nodes (pLN), spleen and thymus. I found that the percentage of Foxp3+ cells among CD4+ cells was significantly higher in wild type compared to KO mice in the thymus. This finding demonstrated the importance of Plau expression for Tregs development in thymus. However, no difference of Foxp3+ Tregs

percentage among CD4+ cells was observed in mLN, pLN and spleen of WT compared to KO mice. This could be explained in several ways. The candidate regulatory gene PLAU was identified during human Treg activation process. Thus PLAU may play a more important role during the process of Treg activation. However, the murine Tregs which I studied here represent naive Tregs. Thus, a difference of Foxp3 expression may be observed after activation in mLN, pLN and spleen of WT and KO. Therefore, further studies will be required to determine the relationship of Plau and Foxp3 in mice for the activation of Treg cells in mLN, pLN and spleen.

7 Publication which resulted from this thesis work

A manuscript is in preparation to publish the results described here. The latest version of this manuscript is provided as a separate document.

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