Mouse models for the study of fate and function of innate lymphoid cells

Cording, Sascha; Medvedovic, Jasna; Lécuyer, Emelyne; Aychek, Tegest; Déjardin, François; Eberl, Gérard

doi:10.1002/eji.201747388

Cited by 24 publications

(18 citation statements)

References 108 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The IFN-␥-producing CCR6 Ϫ NCR1 Ϫ ROR␥t ϩ ILC3 subset cells have been implicated in microbial interactions with the host. Many intestinal ROR␥t ϩ ILC3s can be negative for both NCR1 and CCR6 (52,78). ILC3s are extremely flexible and can produce different cytokine profiles in response to signals from local tissues (54,58,60,61).…”

Section: Discussionmentioning

confidence: 99%

Evasion of Innate Lymphoid Cell-Regulated Gamma Interferon Responses by Chlamydia muridarum To Achieve Long-Lasting Colonization in Mouse Colon

et al. 2020

View full text Add to dashboard Cite

Revealing the mechanisms by which bacteria establish long-lasting colonization in the gastrointestinal tract is an area of intensive investigation. The obligate intracellular bacterium Chlamydia is known to colonize mouse colon for long periods. A colonization-deficient mutant strain of this intracellular bacterium is able to regain long-lasting colonization in gamma interferon (IFN-γ) knockout mice following intracolon inoculation. We now report that mice deficient in conventional T lymphocytes or recombination-activating gene (Rag) failed to show rescue of mutant colonization. Nevertheless, antibody depletion of IFN-γ or genetic deletion of interleukin 2 (IL-2) receptor common gamma chain in Rag-deficient mice did rescue mutant colonization. These observations suggest that colonic IFN-γ, responsible for inhibiting the intracellular bacterial mutant, is produced by innate lymphoid cells (ILCs). Consistently, depletion of NK1.1+ cells in Rag-deficient mice both prevented IFN-γ production and rescued mutant colonization. Furthermore, mice deficient in transcriptional factor RORγt, but not chemokine receptor CCR6, showed full rescue of the long-lasting colonization of the mutant, indicating a role for group 3-like ILCs. However, the inhibitory function of the responsible group 3-like ILCs was not dependent on the natural killer cell receptor (NCR1), since NCR1-deficient mice still inhibited mutant colonization. Consistently, mice deficient in the transcriptional factor T-bet only delayed the clearance of the bacterial mutant without fully rescuing the long-lasting colonization of the mutant. Thus, we have demonstrated that the obligate intracellular bacterium Chlamydia maintains its long-lasting colonization in the colon by evading IFN-γ from group 3-like ILCs.

show abstract

Section: Discussionmentioning

confidence: 99%

Evasion of Innate Lymphoid Cell-Regulated Gamma Interferon Responses by Chlamydia muridarum To Achieve Long-Lasting Colonization in Mouse Colon

et al. 2020

View full text Add to dashboard Cite

show abstract

“…LTi cells assist the formation of lymphoid organs in response to TNF-α and lymphotoxin-β stimulation during embryogenesis. Postnatally, they can also produce IL-17A and IL-22 to defend the gastrointestinal tract against pathogens 34 . ILC3 exist mainly in the intestinal mucosal tissue, playing an important role in mucosal homeostasis and inflammatory responses.…”

Section: Innate Lymphoid Cellsmentioning

confidence: 99%

ILC3 function as a double-edged sword in inflammatory bowel diseases

et al. 2019

View full text Add to dashboard Cite

Inflammatory bowel diseases (IBD), composed mainly of Crohn’s disease (CD) and ulcerative colitis (UC), are strongly implicated in the development of intestinal inflammation lesions. Its exact etiology and pathogenesis are still undetermined. Recently accumulating evidence supports that group 3 innate lymphoid cells (ILC3) are responsible for gastrointestinal mucosal homeostasis through moderate generation of IL-22, IL-17, and GM-CSF in the physiological state. ILC3 contribute to the progression and aggravation of IBD while both IL-22 and IL-17, along with IFN-γ, are overexpressed by the dysregulation of NCR − ILC3 or NCR + ILC3 function and the bias of NCR + ILC3 towards ILC1 as well as regulatory ILC dysfunction in the pathological state. Herein, we feature the group 3 innate lymphoid cells’ development, biological function, maintenance of gut homeostasis, mediation of IBD occurrence, and potential application to IBD therapy.

show abstract

“…Despite progress in the generation of genetically modified mice, specific targeting of ILCs remains a major challenge in the field because of the large overlap in gene expression between ILCs and T cells as well as other immune cells. Since a systematic review of genetic models for the investigation of ILC function was recently published ( 243 ), we aim to focus the discussion on NK cell receptor (NKR) + ILCs that comprise conventional NK cells, ILC1s, and CCR6 − ILC3s. Concerning NKR + ILCs, specific targeting of each subset is further complicated by shared receptors such as NKG2D, NKp46, and NK1.1 and TFs such as T-bet, NFIL3, or TOX within NKR + ILCs, making them alone not a suitable target ( 141 ).…”

Section: Specific Targeting To Uncover Functional Specialization Of Gmentioning

confidence: 99%

NK Cell Development in Times of Innate Lymphoid Cell Diversity

2020

View full text Add to dashboard Cite

After being described in the 1970s as cytotoxic cells that do not require MHC-dependent pre-activation, natural killer (NK) cells remained the sole member of innate lymphocytes for decades until lymphoid tissue-inducer cells in the 1990s and helper-like innate lymphoid lineages from 2008 onward completed the picture of innate lymphoid cell (ILC) diversity. Since some of the ILC members, such as ILC1s and CCR6 − ILC3s, share specific markers previously used to identify NK cells, these findings provoked the question of how to delineate the development of NK cell and helper-like ILCs and how to properly identify and genetically interfere with NK cells. The description of eomesodermin (EOMES) as a lineage-specifying transcription factor of NK cells provided a candidate that may serve as a selective marker for the genetic targeting and identification of NK cells. Unlike helper-like ILCs, NK cell activation is, to a large degree, regulated by the engagement of activating and inhibitory surface receptors. NK cell research has revealed some elegant mechanisms of immunosurveillance, coined "missing-self" and "induced-self" recognition, thus complementing "non-self recognition", which is predominantly utilized by adaptive lymphocytes and myeloid cells. Notably, the balance of activating and inhibitory signals perceived by surface receptors can be therapeutically harnessed for anti-tumor immunity mediated by NK cells. This review aims to summarize the similarities and the differences in development, function, localization, and phenotype of NK cells and helper-like ILCs, with the purpose to highlight the unique feature of NK cell development and regulation.

show abstract

Mouse models for the study of fate and function of innate lymphoid cells

Cited by 24 publications

References 108 publications

Evasion of Innate Lymphoid Cell-Regulated Gamma Interferon Responses by Chlamydia muridarum To Achieve Long-Lasting Colonization in Mouse Colon

Evasion of Innate Lymphoid Cell-Regulated Gamma Interferon Responses by Chlamydia muridarum To Achieve Long-Lasting Colonization in Mouse Colon

ILC3 function as a double-edged sword in inflammatory bowel diseases

NK Cell Development in Times of Innate Lymphoid Cell Diversity

Contact Info

Product

Resources

About