Article,
Type 1 immunity enables neonatal thymic ILC1 production
Contributors
Tougaard, Peter
0000-0003-1304-4152
(Corresponding author)
[1]
[2]
Huysentruyt, Jelle
0000-0001-8192-3031
[1]
[2]
Verstraeten, Bruno
0000-0003-3573-1463
[1]
[2]
Vetters, Jessica
0000-0001-5817-0086
[1]
[2]
Taghon, Tom
0000-0002-5781-0288
[1]
Leclercq, Georges
0000-0002-1691-5294
[1]
Vandenabeele, Peter
0000-0001-5285-9835
(Corresponding author)
[1]
[2]
Affiliations
- [1] Canc Res Inst Ghent CRIG, Ghent, Belgium [NORA names: Belgium; Europe, EU; OECD];
- [2] UGent VIB, Ctr Inflammat Res, Cell Death & Inflammat Unit, Ghent, Belgium [NORA names: Belgium; Europe, EU; OECD];
- [3] Univ Copenhagen, LEO Fdn Skin Immunol Res Ctr, Dept Immunol & Microbiol, Copenhagen, Denmark [NORA names: KU University of Copenhagen; University; Denmark; Europe, EU; Nordic; OECD]
Abstract
Acute thymic atrophy occurs following type 1 inflammatory conditions such as viral infection and sepsis, resulting in cell death and disruption of T cell development. However, the impact type 1 immunity has on thymic-resident innate lymphoid cells (ILCs) remains unclear. Single-cell RNA sequencing revealed neonatal thymic-resident type 1 ILCs (ILC1s) as a unique and immature subset compared to ILC1s in other primary lymphoid organs. Culturing murine neonatal thymic lobes with the type 1 cytokines interleukin-12 (IL-12) and IL-18 resulted in a rapid expansion and thymic egress of KLRG1(+)CXCR6(+) cytotoxic ILC1s. Live imaging showed the subcapsular thymic localization and exit of ILC1s following IL-12 + IL-18 stimulation. Similarly, murine cytomegalovirus infection in neonates resulted in thymic atrophy and subcapsular localization of thymic-resident ILC1s. Neonatal thymic grafting revealed that type 1 inflammation enhances the homing of cytokine-producing thymus-derived ILC1s to the liver and peritoneal cavity. Together, we show that type 1 immunity promotes the expansion and peripheral homing of thymic-derived ILC1s.
