Type 1 immunity enables neonatal thymic ILC1 production

Peter Tougaard; Mario R. Pérez; Wolf Steels; Jelle Huysentruyt; Bruno Verstraeten; Jessica Vetters; Tatyana Divert; Amanda Gonçalves; Ria Roelandt; Nozomi Takahashi; Sophie Janssens; Terkild B. Buus; Tom Taghon; Georges Leclercq; Peter Vandenabeele

doi:10.1126/sciadv.adh5520

Type 1 immunity enables neonatal thymic ILC1 production

Peter Tougaard, Mario R. Pérez, Wolf Steels, Jelle Huysentruyt, Bruno Verstraeten, Jessica Vetters, Tatyana Divert, Amanda Gonçalves, Ria Roelandt, Nozomi Takahashi, Sophie Janssens, Terkild B. Buus, Tom Taghon, Georges Leclercq, Peter Vandenabeele

Skin Immunology Research Center

Research output: Contribution to journal › Journal article › Research › peer-review

5 Citations (Scopus)

19 Downloads (Pure)

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.

Original language	English
Article number	eadh5520
Journal	Science Advances
Volume	10
Issue number	3
Number of pages	17
ISSN	2375-2548
DOIs	https://doi.org/10.1126/sciadv.adh5520
Publication status	Published - 2024

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10.1126/sciadv.adh5520Licence: CC BY-NC

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@article{1c20727cd2994b0ea61f3f0124b23c2e,

title = "Type 1 immunity enables neonatal thymic ILC1 production",

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.",

author = "Peter Tougaard and P{\'e}rez, {Mario R.} and Wolf Steels and Jelle Huysentruyt and Bruno Verstraeten and Jessica Vetters and Tatyana Divert and Amanda Gon{\c c}alves and Ria Roelandt and Nozomi Takahashi and Sophie Janssens and Buus, {Terkild B.} and Tom Taghon and Georges Leclercq and Peter Vandenabeele",

year = "2024",

doi = "10.1126/sciadv.adh5520",

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T1 - Type 1 immunity enables neonatal thymic ILC1 production

AU - Tougaard, Peter

AU - Pérez, Mario R.

AU - Steels, Wolf

AU - Huysentruyt, Jelle

AU - Verstraeten, Bruno

AU - Vetters, Jessica

AU - Divert, Tatyana

AU - Gonçalves, Amanda

AU - Roelandt, Ria

AU - Takahashi, Nozomi

AU - Janssens, Sophie

AU - Buus, Terkild B.

AU - Taghon, Tom

AU - Leclercq, Georges

AU - Vandenabeele, Peter

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

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