Figure 5. Role of RORγt in thymopoiesis.

CD4^-CD8^-CD25^-CD44⁺ (DN1) cells differentiate via DN2, DN3, DN4 into immature single positive (ISP) cells (CD3^-CD4^-CD8^low). These cells subsequently differentiate into CD3⁺CD4⁺CD8⁺, DP thymocytes. RORγt, as well as Bcl-X_L, are induced during the ISP-DP transition and again down-regulated during the differentiation of DP into CD4⁺ and CD8⁺ single positive cells. RORγt promotes the differentiation of ISP into DP cells and positively regulates the expression of the anti-apoptotic gene Bcl-X_L. The latter enhances cell survival that subsequently promotes TCR rearrangements. Lack of RORγt expression inhibits the ISP-DP transition and reduces expression of Bcl-X_L in DP thymocytes. The latter results in accelerated apoptosis, reduced lifespan of DP thymocytes and, consequently, impaired TCRα rearrangements