To investigate how TReg cells orchestrate tissue- and cell type-specific suppression, the authors assessed the active kinases in TReg cells compared with effector T cells following activation. Among the highly active kinases in TReg cells, CK2 (encoded by Csnk2) showed the greatest difference in activity between the two T cell subsets in both mice and humans. On the basis of this observation, the authors generated mutant mice with a selective deletion of Csnk2b in TReg cells. TReg cell-specific deficiency of CK2β did not affect thymic T cell development or TReg cell homeostasis in the periphery. However, compared with control mice, mutant mice had increased cell numbers in the spleen and lymph nodes, in particular in the tracheal lymph nodes. Most strikingly, there was a massive infiltration of immune cells into the lungs. The immunopathology worsened with age but it did not reach the extent of organ-wide immunopathology that is observed in TReg cell-deficient scurfy mice.
Further analysis of the lung infiltrate in the CK2β-mutant mice revealed that it comprised mainly TH2 cells (marked by expression of GATA3), with only a marginal increase in the number of TH1 and TH17 cells compared with control mice. Notably, under steady-state conditions, mice with CK2β-deficient TReg cells had increased titres of IgE (which is induced by the TH2 cell cytokine interleukin-4) in the serum. Together, these data suggest that TReg cell-specific deficiency of CK2β results in the spontaneous development of an uncontrolled TH2 cell-driven immune response.
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