Poster Presentation Asia-Pacific Vaccine and Immunotherapy Congress 2023

Contrasting roles of NKG7 and TGFβ during Leishmania donovani infection (#113)

Jinrui Na 1 2 , Fabian Rivera 1 , Christian Engwerda 1
  1. QIMR Berghofer, Brisbane
  2. Faculty of Medicine, University of Queensland, Brisbane

Visceral leishmaniasis (VL) refers to severe, systemic manifestations of disease caused by Leishmania protozoan parasites.   The disease remains endemic across large parts of the developing world. Increasing resistance to existing chemotherapies and the lack of effective vaccines drive the need for novel avenues of treatments, such as immunotherapy. During VL, a robust CD4+ Th1 cell-mediated response is required for effective clearance of the parasite, and dysregulation of this response leads to chronic infection. Natural Killer Granule Protein 7 (NKG7), a 17kDa transmembrane protein, has been found to be highly upregulated in CD4+ T cells under chronic inflammatory environments. Despite being first described in 19931, the function of NKG7 remained unexplored till recent times. We have previously shown that NKG7 plays a critical role in driving Th1 cell-mediated inflammation during VL2, and current CD4+ T cell-specific NKG7 ko models identified multiple cell-intrinsic functional deficiencies, and ongoing experiments are aimed to identify essential cellular processes that are affected by the loss of NKG7. Furthermore, we have previously identified TGFβ as a strong suppressor of NKG7 expression in CD4+ T cells2, prompting a need to understand the nature of their interactions. Current studies using T cell-specific ko of Transforming Growth Factor beta (TGFβ) signaling models showed a strong enhancement of NKG7 expression on CD4+ T cells during VL, alongside considerable improvements in the Th1 cell-mediated immune response. These results were expanded upon using Bulk RNAseq on CD4+ T cells to identify gene networks affected by the loss of TGFβ signaling, with the ultimate goal of establishing the nature of the relationship between TGFβ and NKG7.

  1. Turman, M.A., Yabe, T., McSherry, C., Bach, F.H. & Houchins, J.P. Characterization of a novel gene (NKG7) on human chromosome 19 that is expressed in natural killer cells and T cells. Hum Immunol 36, 34-40 (1993).
  2. Ng, S.S. et al. The NK cell granule protein NKG7 regulates cytotoxic granule exocytosis and inflammation. Nature Immunology 21, 1205-1218 (2020).