Development of group-3 innate lymphoid cells via Tox 2-dependent pathway in gut

• Published in: The Journal of immunology (1950) 2019-05, Vol.202 (1_Supplement), p.53-53.1
• Main Authors: Das, Arundhoti, Wang, Yueqiang, Lu, Xiaoxiao, Harly, Christelle, Kaye, Jonathan, Bhandoola, Avinash
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.202.Supp.53.1

Innate lymphoid cells (ILCs) are immune cells that lack specific antigen receptors but possess similar effector functions as T cells. Interestingly, ILCs and T cells express many of the same transcription factors. One such factor is TOX, a sequence non-specific nuclear transcriptional regulator that is crucial for development of both CD4 T cells and ILCs. TOX-deficient mice have significantly reduced number of early innate lymphoid progenitors (EILP) and ILC progenitors (ILCP). Consequently, the mature NK cells, ILC1, ILC2 and ILC3 subsets are greatly reduced in Tox−/− mice. Interestingly ILC3 in gut are not affected by the absence of TOX. We have discovered that TOX2, another member of the TOX family of HMG-box proteins, is highly expressed in ILC precursors. We generated Tox2−/− mice and found they have reduced ILC3 in gut; however, ILC3 cells in spleen or lymph node are intact. We also observed putative ILCP in fetal gut were significantly reduced in Tox2−/− mice. Hence our results indicate the existence of at least two pathways of ILC development: a central pathway in bone marrow and fetal liver that is TOX dependent; and a peripheral pathway of development of ILC3 in gut that requires TOX2. Additionally, we observed that TOX2 is not required for development of T cells. However, Tox2−/− mice showed higher frequency of PD1 expressing CD8 effector memory cells. Tox2−/− mice also showed greater Th1 responses in vitro. Together, our results suggest that TOX is important centrally, for T cells and ILCs; whereas TOX2 is important for peripheral ILC3 generation or maintenance, and may further play an important role in effector T cells in tissues.