HOIL1 regulates group 2 innate lymphoid cell numbers and type 2 inflammation in the small intestine

Wood, Matthew J.; Marshall, Jeffrey N.; Hartley, Victoria L.; Liu, Ta‐Chiang; Iwaï, Kazuhiro; Stappenbeck, Thaddeus S

doi:10.1038/s41385-022-00520-z

Cited by 4 publications

(8 citation statements)

References 49 publications

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“…The frequency of intestinal CD90 - ILC2 was enhanced in Hoil1 -/- mice, a mouse model defined by microbe-driven intestinal inflammation (Wood et al ., 2022). In comparison, an alteration of CD90 + ILC2 prevalence was not observed in these mice (Wood et al ., 2022). Furthermore, Aspergillus fumigatus -induced inflammation also leads to the promoted occurrence of pulmonary CD4 + T cells with low expression of CD90 (Ulrich et al ., 2022).…”

Section: Resultsmentioning

confidence: 99%

“…Such modified expression of CD90 upon exposure to pathogens is not without precedent. The frequency of intestinal CD90 - ILC2 was enhanced in Hoil1 -/- mice, a mouse model defined by microbe-driven intestinal inflammation (Wood et al ., 2022). In comparison, an alteration of CD90 + ILC2 prevalence was not observed in these mice (Wood et al ., 2022).…”

Section: Discussionmentioning

confidence: 99%

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CD90 is not constitutively expressed in functional innate lymphoid cells

Schroeder

Zabinski

Neves

et al. 2021

Preprint

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Huge progress has been made in understanding the biology of innate lymphoid cells (ILC) by adopting several well-known concepts of T cell biology. As such flow cytometry gating strategies and markers, such as CD90, to identify ILC were discovered. Here we report that most non-NK intestinal ILC have a high expression of CD90 as expected, but surprisingly some have only a low or even no expression of this marker. CD90-negative CD127+ ILC were identified among all ILC subsets in the gut. CD90-negative cLP ILC2 were frequent at steady state. The frequency of CD90-negative CD127+ ILC was dependent on stimulatory cues in vitro and in vivo, and CD90-negative CD127+ ILC played a functional role as a source of IL-13, IFNγ and IL-17A at steady state and upon dextran sulphate sodium-elicited colitis. Hence, this study highlights for the first time that CD90 is not constitutively expressed by functional ILC in the gut.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

CD90 is not constitutively expressed in functional innate lymphoid cells

Schroeder

Zabinski

Neves

et al. 2021

Preprint

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show abstract

“…Such modified expression of CD90 upon exposure to pathogens is not without precedent. The frequency of intestinal CD90 - ILC2 was enhanced in Hoil1 -/- mice, a mouse model defined by microbe-driven intestinal inflammation ( 62 ). In comparison, an alteration of CD90 + ILC2 prevalence was not observed in these mice ( 62 ).…”

Section: Discussionmentioning

confidence: 99%

“…The frequency of intestinal CD90 - ILC2 was enhanced in Hoil1 -/- mice, a mouse model defined by microbe-driven intestinal inflammation ( 62 ). In comparison, an alteration of CD90 + ILC2 prevalence was not observed in these mice ( 62 ). Furthermore, Aspergillus fumigatus -induced inflammation also leads to the promoted occurrence of pulmonary CD4 + T cells with low expression of CD90 ( 63 ).…”

Section: Discussionmentioning

confidence: 99%

CD90 is not constitutively expressed in functional innate lymphoid cells

Schroeder

Beattie

et al. 2023

Front. Immunol.

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Huge progress has been made in understanding the biology of innate lymphoid cells (ILC) by adopting several well-known concepts in T cell biology. As such, flow cytometry gating strategies and markers, such as CD90, have been applied to indentify ILC. Here, we report that most non-NK intestinal ILC have a high expression of CD90 as expected, but surprisingly a sub-population of cells exhibit low or even no expression of this marker. CD90-negative and CD90-low CD127+ ILC were present amongst all ILC subsets in the gut. The frequency of CD90-negative and CD90-low CD127+ ILC was dependent on stimulatory cues in vitro and enhanced by dysbiosis in vivo. CD90-negative and CD90-low CD127+ ILC were a potential source of IL-13, IFNγ and IL-17A at steady state and upon dysbiosis- and dextran sulphate sodium-elicited colitis. Hence, this study reveals that, contrary to expectations, CD90 is not constitutively expressed by functional ILC in the gut.

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“…Mice. Hoil1 -/-(B6.Cg-Hoil1 tm1Kiwa ), Rag1 -/-Hoil1 -/and Hoil1 -/-Il4ra DIEC mice have been described previously (24,26,45). Wild type control mice were either Hoil1 +/+ littermates or C56BL/6 mice from our colony.…”

Section: Methodsmentioning

confidence: 99%

HOIL1 Regulates Group 3 Innate Lymphoid Cells in the Colon and Protects against Systemic Dissemination, Colonic Ulceration, and Lethality from Citrobacter rodentium Infection

Hartley,

Qaqish,

Wood

et al. 2023

The Journal of Immunology

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Heme-oxidized IRP2 ubiquitin ligase-1 (HOIL1)-deficient patients experience chronic intestinal inflammation and diarrhea as well as increased susceptibility to bacterial infections. HOIL1 is a component of the linear ubiquitin chain assembly complex that regulates immune signaling pathways, including NF-κB–activating pathways. We have shown previously that HOIL1 is essential for survival following Citrobacter rodentium gastrointestinal infection of mice, but the mechanism of protection by HOIL1 was not examined. C. rodentium is an important murine model for human attaching and effacing pathogens, enteropathogenic and enterohemorrhagic Escherichia coli that cause diarrhea and foodborne illnesses and lead to severe disease in children and immunocompromised individuals. In this study, we found that C. rodentium infection resulted in severe colitis and dissemination of C. rodentium to systemic organs in HOIL1-deficient mice. HOIL1 was important in the innate immune response to limit early replication and dissemination of C. rodentium. Using bone marrow chimeras and cell type–specific knockout mice, we found that HOIL1 functioned in radiation-resistant cells and partly in radiation-sensitive cells and in myeloid cells to limit disease, but it was dispensable in intestinal epithelial cells. HOIL1 deficiency significantly impaired the expansion of group 3 innate lymphoid cells and their production of IL-22 during C. rodentium infection. Understanding the role HOIL1 plays in type 3 inflammation and in limiting the pathogenesis of attaching and effacing lesion-forming bacteria will provide further insight into the innate immune response to gastrointestinal pathogens and inflammatory disorders.

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HOIL1 regulates group 2 innate lymphoid cell numbers and type 2 inflammation in the small intestine

Cited by 4 publications

References 49 publications

CD90 is not constitutively expressed in functional innate lymphoid cells

CD90 is not constitutively expressed in functional innate lymphoid cells

CD90 is not constitutively expressed in functional innate lymphoid cells

HOIL1 Regulates Group 3 Innate Lymphoid Cells in the Colon and Protects against Systemic Dissemination, Colonic Ulceration, and Lethality from Citrobacter rodentium Infection

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