The regulation and differentiation of regulatory T cells and their dysfunction in autoimmune diseases.

The discovery of FOXP3 regulatory T (T) cells as a distinct cell lineage with a central role in regulating immune responses provided a deeper understanding of self-tolerance. The transcription factor FOXP3 serves a key role in T cell lineage determination and maintenance, but is not sufficient to enable the full potential of T cell suppression, indicating that other factors orchestrate the fine-tuning of T cell function. Moreover, FOXP3-independent mechanisms have recently been shown to contribute to T cell dysfunction.

Regulatory T cells in peripheral tissue tolerance and diseases.

Maintenance of peripheral tolerance by CD4Foxp3 regulatory T cells (Tregs) is essential for regulating autoreactive T cells. The loss of function of Foxp3 leads to autoimmune disease in both animals and humans. An example is the rare, X-linked recessive disorder known as IPEX (Immune Dysregulation, Polyendocrinopathy, Enteropathy X-linked) syndrome.

Hedgehog-induced ZFYVE21 promotes chronic vascular inflammation by activating NLRP3 inflammasomes in T cells.

The zinc finger protein ZFYVE21 is involved in immune signaling. Using humanized mouse models, primary human cells, and patient samples, we identified a T cell-autonomous role for ZFYVE21 in promoting chronic vascular inflammation associated with allograft vasculopathy. Ischemia-reperfusion injury (IRI) stimulated endothelial cells to produce Hedgehog (Hh) ligands, which in turn induced the production of ZFYVE21 in a population of T memory cells with high amounts of the Hh receptor PTCH1 (PTCH cells, CD3CD4CD45ROPTCH1PD-1), vigorous recruitment to injured endothelia, and increased effector responses in vivo.

CD4 T cell lymphopenia predicts mortality from Pneumocystis pneumonia in kidney transplant patients.

Background: Pneumocystis jirovecii pneumonia (PcP) remains a life-threatening opportunistic infection after solid organ transplantation, even in the era of Pneumocystis prophylaxis. The association between risk of developing PcP and low CD4 T cell counts has been well established. However, it is unknown whether lymphopenia in the context of post-renal transplant PcP increases the risk of mortality.

A Novel Hybrid Cytokine IL233 Mediates regeneration following Doxorubicin-Induced Nephrotoxic Injury.

Kidney injury, whether due to ischemic insults or chemotherapeutic agents, is exacerbated by inflammation, whereas Tregs are protective. We recently showed that IL-2 and IL-33, especially as a hybrid cytokine (IL233 - bearing IL-2 and IL-33 activities in one molecule), potentiated Tregs and group 2 innate lymphoid cells (ILC2) to prevent renal injury. Recent studies have indicated a reparative function for Tregs and ILC2.