Testosterone Attenuates Group 2 Innate Lymphoid Cell-Mediated Airway Inflammation

Cephus, Jacqueline; Stier, Matthew T.; Fuseini, Hubaida; Yung, Jeffrey A.; Toki, Shinji; Bloodworth, Melissa H.; Zhou, Weisong; Goleniewska, Kasia; Zhang, Jian; Garon, Sarah L.; Hamilton, Robert G.; Poloshukin, Vasiliy V.; Boyd, Kelli L.; Peebles, R. Stokes; Newcomb, Dawn C.

doi:10.1016/j.celrep.2017.10.110

Cited by 220 publications

(307 citation statements)

References 34 publications

Supporting

Mentioning

257

Contrasting

Unclassified

Order By: Relevance

“…Investigation of the role of sex hormones and ERα showed that the KLRG1 − subset is most prominent when androgen levels are low (as in normal females) but does not depend on endogenous estrogens or ERα signaling. Our data are consistent withrecentreportsthatlungILC2numbersinmalesareattenuated by AR signaling (14, 15). The presence of a functional lung-resident KLRG1 − ILC2 subset in females may alter the magnitude or quality of type 2 inflammation upon allergen or pathogen insult to the respiratory tract.…”

Section: Discussionsupporting

confidence: 92%

“…Despite this, there are few examples of significant sex differences in numbers of innate immune cells in homeostasis. Prior reports have shown that female mice have higher numbers of lung-resident ILC2s, including a prominent subset lacking KLRG1 (14, 15). In this study, we have shown that the KLRG1 − subset is a very minor population at 3 wk of age in both sexes, but increases after reproductive age (by 8–12 wk) in females but not in males.…”

Section: Discussionmentioning

confidence: 99%

“…ILC2s may contribute to human disease pathology as they are expanded in the blood, respiratory tract, or skin of individuals with asthma, chronic rhinosinusitis, idiopathic pulmonary fibrosis, and atopic dermatitis (18, 33). Importantly, sex differences in human blood ILC2s in asthma patients were recently reported (15). …”

Section: Introductionmentioning

confidence: 95%

“…Recent studies have shown that sex hormone levels regulate tissue-resident populations of group 2 innate lymphocytes (ILC2s) in homeostasis. AR activity and endogenous androgens reduce numbers of ILC2s in the lung and visceral adipose tissue of male mice (14, 15), whereas ERα activity and endogenous estrogens increase numbers of ILC2s in the female uterus (16). The ER and AR control epigenetic and transcriptional programs through their activity as ligand-dependent DNA-binding factors (9, 10).…”

Section: Introductionmentioning

confidence: 99%

“…Lung-resident ILC2s are well studied in murine models of asthma and infection, where they have been linked to initiation or perpetuation of type 2 responses and tissue repair (27–31). Increased numbers of IL-5– and IL-13–producing ILC2s in females were observed in models of allergic lung inflammation, suggesting that baseline sex differences in ILC2 numbers contribute to the magnitude of the inflammatory response (15, 32). ILC2s may contribute to human disease pathology as they are expanded in the blood, respiratory tract, or skin of individuals with asthma, chronic rhinosinusitis, idiopathic pulmonary fibrosis, and atopic dermatitis (18, 33).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

A Major Population of Functional KLRG1– ILC2s in Female Lungs Contributes to a Sex Bias in ILC2 Numbers

et al. 2018

View full text Add to dashboard Cite

Humans show significant sex differences in the incidence and severity of respiratory diseases, including asthma and virus infection. Sex hormones contribute to the female sex bias in type 2 inflammation associated with respiratory diseases, consistent with recent reports that female lungs harbor greater numbers of GATA-3–dependent group 2 innate lymphoid cells (ILC2s). In this study, we determined whether sex hormone levels govern sex differences in the numbers, phenotype, and function of ILC2s in the murine lung and bone marrow (BM). Our data show that lungs of female mice harbor significantly greater ILC2 numbers in homeostasis, in part due to a major subset of ILC2s lacking killer-cell lectin like receptor G1 (KLRG1), a population largely absent in male lungs. The KLRG1− ILC2s were capable of type 2 cytokine production and increased with age after sexual maturity, suggesting that a unique functional subset exists in females. Experiments with gonadectomized mice or mice bearing either global or lymphocyte restricted estrogen receptor α (Esr1) deficiency showed that androgens rather than estrogens regulated numbers of the KLRG1− ILC2 subset and ILC2 functional capacity in the lung and BM, as well as levels of GATA-3 expression in BM ILC2s. Furthermore, the frequency of BM PLZF+ ILC precursors was higher in males and increased by excess androgens, suggesting that androgens act to inhibit the transition of ILC precursors to ILC2s. Taken together, these data show that a functional subset of KLRG1− ILC2s in females contributes to the sex bias in lung ILC2s that is observed after reproductive age.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

A Major Population of Functional KLRG1– ILC2s in Female Lungs Contributes to a Sex Bias in ILC2 Numbers

et al. 2018

View full text Add to dashboard Cite

show abstract

Identification of Group 2 Innate Lymphoid Cells in Mouse Lung, Liver, Small Intestine, Bone Marrow, and Mediastinal and Mesenteric Lymph Nodes

et al. 2019

View full text Add to dashboard Cite

Innate lymphoid cells (ILCs) are a heterogeneous family of lymphocytes that populate barrier and non‐barrier tissues. ILCs regulate immune responses to pathogens and commensals but also sustain metabolic homeostasis, tissue remodeling after injury and establish dialogue with the nervous system. ILCs rapidly become activated in the absence of adaptive antigen receptors by responding to signaling molecules provided by hematopoietic or non‐hematopoietic cells. Here we provide protocols designed for processing the lung, liver, small intestine, bone marrow, mediastinal and mesenteric lymph nodes in order to obtain a purified leukocyte fraction of cells, in which ILC2 enrichment is optimized. In addition, we describe in detail the methodologies used to activate ILC2s and the assays necessary for the detection of their effector cytokines. We highlight the differences in ILC2 characterization within distinct tissues that we have recently identified. © 2019 by John Wiley & Sons, Inc.

show abstract

Sex differences regulate immune responses in experimental autoimmune encephalomyelitis and multiple sclerosis

Ryan

Mills

2021

Eur J Immunol

View full text Add to dashboard Cite

MS is an autoimmune disease of the CNS that afflicts over 2.5 million people worldwide. There are striking sex differences in the susceptibility to and progression of this disease in humans. Females are twice as likely to develop MS than males, whereas disease progression and disability is more rapid in males compared with females; however, the latter is still controversial. There is growing evidence, mainly from animal models, that innate and adaptive immune responses are different in males and females, and that this can influence the outcome of a range of diseases including infection, cancer, and autoimmunity. Since MS is an immune-mediated disease, sex differences in pathogenic immune responses may account for some of the differences in susceptibility to and progression seen in men versus women. Indeed, data from the mouse model of MS, EAE, have already provided some evidence that female mice have earlier disease onset associated with stronger Th17 responses. This review will discuss the possible immunological basis of sex differences in susceptibility and disease outcome in EAE and MS and how a better understanding of sex differences in the responses to disease-modifying therapies may lead to improved patient treatment.

show abstract

Testosterone Attenuates Group 2 Innate Lymphoid Cell-Mediated Airway Inflammation

Cited by 220 publications

References 34 publications

A Major Population of Functional KLRG1– ILC2s in Female Lungs Contributes to a Sex Bias in ILC2 Numbers

A Major Population of Functional KLRG1– ILC2s in Female Lungs Contributes to a Sex Bias in ILC2 Numbers

Identification of Group 2 Innate Lymphoid Cells in Mouse Lung, Liver, Small Intestine, Bone Marrow, and Mediastinal and Mesenteric Lymph Nodes

Sex differences regulate immune responses in experimental autoimmune encephalomyelitis and multiple sclerosis

Contact Info

Product

Resources

About