OMIP‐055: Characterization of Human Innate Lymphoid Cells from Neonatal and Peripheral Blood

Abstract Here we investigated the role of NFAT-interacting protein (NIP)-45, an Interleukin (IL)-4 inducing Transcription Factor, and its impact on the differentiation of Group 2 Innate -Lymphoid -Cells (ILC2s) in the pathogenesis of asthma. NIP45, a transcription factor regulating NFATc1 activity, mRNA was found to be induced in the Peripheral Blood mononuclear cells (PMBCs) of asthmatic pre-school children with allergies and in the peripheral blood CD4+ T cells from adult asthmatic patients. In PBMCs of asthmatic and control children, NIP45 mRNA directly correlated with NFATc1 but not with T-bet. Targeted deletion of NIP45 in mice resulted in a protective phenotype in experimental asthma with reduced airway mucus production, airway hyperresponsiveness and eosinophils. This phenotype was reversed by intranasal delivery of recombinant r-IL-33. Consistently, ILC2s and not GATA3+ CD4+ T-cells were decreased in the lungs of asthmatic NIP45−/− mice. Reduced cell number spleen ILC2s could be differentiated from NIP45−/− as compared to wild-type mice after in vivo injection of a microcircle-DNA vector expressing IL-25 and decreased cytokines and ILC2 markers in ILC2 differentiated from the bone marrow of NIP45−/− mice. NIP45 thus emerges as a new therapeutic target for the resolution of the airway pathology, down-regulation of ILC2s and mucus production in asthma.

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Multiplexed histology analyses for the phenotypic and spatial characterization of human innate lymphoid cells

Nature Communications ◽

10.1038/s41467-021-21994-8 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Anna Pascual-Reguant ◽

Ralf Köhler ◽

Ronja Mothes ◽

Sandy Bauherr ◽

Daniela C. Hernández ◽

...

Keyword(s):

Immune Responses ◽

Histological Analysis ◽

Plasma Cells ◽

Innate Lymphoid Cells ◽

Lymphoid Cells ◽

Source Analysis ◽

Biological Processes ◽

Analysis Pipeline

AbstractInnate lymphoid cells (ILCs) emerge in the last few years as important regulators of immune responses and biological processes. Although ILCs are mainly known as tissue-resident cells, their precise localization and interactions with the microenvironment are still unclear. Here we combine a multiplexed immunofluorescence technique and a customized computational, open-source analysis pipeline to unambiguously identify CD127+ ILCs in situ and characterize these cells and their microenvironments. Moreover, we reveal the transcription factor IRF4 as a marker for tonsillar ILC3, and identify conserved stromal landmarks characteristic for ILC localization. We also show that CD127+ ILCs share tissue niches with plasma cells in the tonsil. Our works thus provide a platform for multiparametric histological analysis of ILCs to improve our understanding of ILC biology.

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Innate lymphoid cells in peripheral blood of patients with American Cutaneous Leishmaniasis

Experimental Dermatology ◽

10.1111/exd.14351 ◽

2021 ◽

Author(s):

Orquídea L. Rodríguez ◽

Dennis A. Lugo ◽

Maira Cabrera ◽

Martín A. Sánchez ◽

Olga Zerpa ◽

...

Keyword(s):

Cutaneous Leishmaniasis ◽

Peripheral Blood ◽

Innate Lymphoid Cells ◽

Lymphoid Cells ◽

American Cutaneous Leishmaniasis

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Circulating Innate Lymphoid Cells Exhibit Distinctive Distribution During Normal Pregnancy

Reproductive Sciences ◽

10.1007/s43032-021-00834-6 ◽

2022 ◽

Author(s):

Yiran Zhao ◽

Yajie Zhu ◽

Xi Chen ◽

Hui Lin ◽

Ningxin Qin ◽

...

Keyword(s):

Pregnant Women ◽

Peripheral Blood ◽

Progesterone Receptors ◽

Normal Pregnancy ◽

Innate Lymphoid Cells ◽

Sex Hormone ◽

Lymphoid Cells ◽

Hormone Levels ◽

Potential Association ◽

Plasma Estradiol

AbstractOver the past decades, the investigation of innate lymphoid cells (ILCs) has revealed their significance in successful pregnancy. Sex hormones, such as estradiol and progesterone, show specific changes during pregnancy and modulate both adaptive and innate immune systems. ILC subset distribution in peripheral blood of pregnant women and its potential association with sex hormone levels have not been well revealed. Peripheral blood was obtained from healthy non-pregnant, early-pregnant, and late-pregnant women. Radioimmunoassay was performed to measure plasma estradiol and progesterone levels. The levels of type 1 ILCs (ILC1s), type 2 ILCs (ILC2s), type 3 ILCs (ILC3s), and total ILCs as well as estrogen and progesterone receptors of ILC2s in peripheral blood were analyzed using flow cytometry. The proportion of total ILCs and distribution of ILC subsets in peripheral blood changed dynamically during pregnancy. Compared to non-pregnant women, late-pregnant women displayed significantly higher proportion of circulating ILCs, among which ILC2s accounted for the majority in late-pregnant women while a smaller part in others, and ILC3s displayed the opposite. Plasma estradiol and progesterone levels elevated while pregnancy proceeded and the expression of their receptors in ILC2s increased consisted with the proportion of circulating ILC2s. Our work first observed the existence of progesterone receptors in human circulating ILC2s and revealed the distribution pattern of circulating ILC subsets and their interrelation with plasma sex hormone levels during pregnancy. Our results suggested that the estradiol and progesterone levels might partly influence the distribution of circulating ILC subsets and implied the interplay between circulating ILCs and pregnancy.

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