Characterization of Rat ILCs Reveals ILC2 As the Dominant Intestinal Subset

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2020 Mar 7

PMID 32140157

Citations 7

Authors

Ahmed Abidi

Thomas Laurent

Gaelle Beriou

Laurence Bouchet-Delbos

Cynthia Fourgeux

Cedric Louvet

Raja Triki-Marrakchi

Jeremie Poschmann

Regis Josien

Jerome Martin

Affiliations

Soon will be listed here.

Abstract

Innate lymphoid cells (ILCs) are tissue-resident lymphocytes that lack antigen-specific receptors and exhibit innate effector functions such as cytokine production that play an important role in immediate responses to pathogens especially at mucosal sites. Mouse and human ILC subsets have been extensively characterized in various tissues and in blood. In this study, we present the first characterization of ILCs and ILC subsets in rat gut and secondary lymphoid organs using flow cytometry and single cell RNA sequencing. Our results show that phenotype and function of rat ILC subsets are conserved as compared to human and mouse ILCs. However, and in contrast to human and mouse, our study unexpectedly revealed that ILC2 and not ILC3 was the dominant ILC subset in the rat intestinal lamina propria. ILC2 predominance in the gut was independent of rat strain, sex or housing facility. In contrast, ILC3 was the predominant ILC subset in mesenteric lymph nodes and Peyer patches. In conclusion, our study demonstrates that in spite of highly conserved phenotype and function between mice, rat and humans, the distribution of ILC subsets in the intestinal mucosa is dependent on the species likely in response to both genetic and environmental factors.

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References

Fournie G, Cautain B, Xystrakis E, Damoiseaux J, Mas M, Lagrange D . Cellular and genetic factors involved in the difference between Brown Norway and Lewis rats to develop respectively type-2 and type-1 immune-mediated diseases. Immunol Rev. 2002; 184:145-60. DOI: 10.1034/j.1600-065x.2001.1840114.x. View

Goverse G, Labao-Almeida C, Ferreira M, Molenaar R, Wahlen S, Konijn T . Vitamin A Controls the Presence of RORγ+ Innate Lymphoid Cells and Lymphoid Tissue in the Small Intestine. J Immunol. 2016; 196(12):5148-55. DOI: 10.4049/jimmunol.1501106. View

Mackley E, Houston S, Marriott C, Halford E, Lucas B, Cerovic V . CCR7-dependent trafficking of RORγ⁺ ILCs creates a unique microenvironment within mucosal draining lymph nodes. Nat Commun. 2015; 6:5862. PMC: 4354100. DOI: 10.1038/ncomms6862. View

Huang Y, Paul W . Inflammatory group 2 innate lymphoid cells. Int Immunol. 2015; 28(1):23-8. PMC: 4715228. DOI: 10.1093/intimm/dxv044. View

Robinette M, Fuchs A, Cortez V, Lee J, Wang Y, Durum S . Transcriptional programs define molecular characteristics of innate lymphoid cell classes and subsets. Nat Immunol. 2015; 16(3):306-17. PMC: 4372143. DOI: 10.1038/ni.3094. View

Stuart T, Butler A, Hoffman P, Hafemeister C, Papalexi E, Mauck 3rd W . Comprehensive Integration of Single-Cell Data. Cell. 2019; 177(7):1888-1902.e21. PMC: 6687398. DOI: 10.1016/j.cell.2019.05.031. View

Martin J, Chang C, Boschetti G, Ungaro R, Giri M, Grout J . Single-Cell Analysis of Crohn's Disease Lesions Identifies a Pathogenic Cellular Module Associated with Resistance to Anti-TNF Therapy. Cell. 2019; 178(6):1493-1508.e20. PMC: 7060942. DOI: 10.1016/j.cell.2019.08.008. View

Simoni Y, Fehlings M, Kloverpris H, McGovern N, Koo S, Loh C . Human Innate Lymphoid Cell Subsets Possess Tissue-Type Based Heterogeneity in Phenotype and Frequency. Immunity. 2016; 46(1):148-161. PMC: 7612935. DOI: 10.1016/j.immuni.2016.11.005. View

Dutton E, Camelo A, Sleeman M, Herbst R, Carlesso G, Belz G . Characterisation of innate lymphoid cell populations at different sites in mice with defective T cell immunity. Wellcome Open Res. 2018; 2:117. PMC: 5854988. DOI: 10.12688/wellcomeopenres.13199.3. View

10.

Hazenberg M, Spits H . Human innate lymphoid cells. Blood. 2014; 124(5):700-9. DOI: 10.1182/blood-2013-11-427781. View

11.

Sawa S, Cherrier M, Lochner M, Satoh-Takayama N, Fehling H, Langa F . Lineage relationship analysis of RORgammat+ innate lymphoid cells. Science. 2010; 330(6004):665-9. DOI: 10.1126/science.1194597. View

12.

Huang Y, Guo L, Qiu J, Chen X, Hu-Li J, Siebenlist U . IL-25-responsive, lineage-negative KLRG1(hi) cells are multipotential 'inflammatory' type 2 innate lymphoid cells. Nat Immunol. 2014; 16(2):161-9. PMC: 4297567. DOI: 10.1038/ni.3078. View

13.

Zhong C, Zheng M, Zhu J . Lymphoid tissue inducer-A divergent member of the ILC family. Cytokine Growth Factor Rev. 2018; 42:5-12. PMC: 6089680. DOI: 10.1016/j.cytogfr.2018.02.004. View

14.

Benezech C, Jackson-Jones L . ILC2 Orchestration of Local Immune Function in Adipose Tissue. Front Immunol. 2019; 10:171. PMC: 6374325. DOI: 10.3389/fimmu.2019.00171. View

15.

Neill D, Wong S, Bellosi A, Flynn R, Daly M, Langford T . Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity. Nature. 2010; 464(7293):1367-70. PMC: 2862165. DOI: 10.1038/nature08900. View

16.

Wong S, Chin K, Suhaimi F, Fairus A, Ima-Nirwana S . Animal models of metabolic syndrome: a review. Nutr Metab (Lond). 2016; 13:65. PMC: 5050917. DOI: 10.1186/s12986-016-0123-9. View

17.

Bernink J, Peters C, Munneke M, Te Velde A, Meijer S, Weijer K . Human type 1 innate lymphoid cells accumulate in inflamed mucosal tissues. Nat Immunol. 2013; 14(3):221-9. DOI: 10.1038/ni.2534. View

18.

Aleixandre de Artinano A, Miguel Castro M . Experimental rat models to study the metabolic syndrome. Br J Nutr. 2009; 102(9):1246-53. DOI: 10.1017/S0007114509990729. View

19.

Vosshenrich C, Garcia-Ojeda M, Samson-Villeger S, Pasqualetto V, Enault L, Goff O . A thymic pathway of mouse natural killer cell development characterized by expression of GATA-3 and CD127. Nat Immunol. 2006; 7(11):1217-24. DOI: 10.1038/ni1395. View

20.

Wang S, Xia P, Chen Y, Qu Y, Xiong Z, Ye B . Regulatory Innate Lymphoid Cells Control Innate Intestinal Inflammation. Cell. 2017; 171(1):201-216.e18. DOI: 10.1016/j.cell.2017.07.027. View