Androgen and Androgen Receptor as Enhancers of M2 Macrophage Polarization in Allergic Lung Inflammation

Becerra-Díaz, Mireya; Strickland, Ashley B.; Keselman, Aleksander; Heller, Nicola

doi:10.4049/jimmunol.1800352

Cited by 115 publications

(94 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In mouse models, DHT downregulated Th2 inflammation in the lung, but ARs enhanced such inflammation by upregulating M2 macrophage polarisation that induces eosinophil recruitment. 29 In our previous analysis in NHANES, in which there were both a LLOD and a broader range of serum estradiol levels than those in the current study, 10 we found no significant association between serum estradiol and asthma in our main analysis. Although our current finding of an association between a detectable serum estradiol and asthma and reduced FEV 1 /FVC in women, and reduced lung function measures (FEV 1 , FVC…”

Section: Discussioncontrasting

confidence: 69%

Serum free testosterone and asthma, asthma hospitalisations and lung function in British adults

Han

Yan

Yang

et al. 2020

Thorax

View full text Add to dashboard Cite

ObjectiveWe examined the relation between serum-free testosterone and asthma, wheeze, asthma hospitalisations and lung function in older adults.DesignCross-sectional study.SettingUK.Participants256 419 adults aged 40 to 69 years, recruited from 2006 to 2010.Main outcome measuresMultivariable logistic or linear regression was used for the analysis of free testosterone and physician-diagnosed asthma, current wheeze, asthma hospitalisations and lung function measures, which was adjusted for serum estradiol, smoking status and other covariates.ResultsFree testosterone levels above the lowest quartile (Q1) were significantly associated with lower odds of asthma in both women (adjusted OR (aOR) for Q4 (the highest quartile) versus Q1=0.67, 95% CI=0.64 to 0.71) and men (aOR for Q4 versus Q1=0.87, 95% CI=0.82 to 0.91). Among subjects with asthma, free testosterone levels above Q1 were significantly associated with lower odds of current wheeze in women (aOR range=0.78 to 0.87), and free testosterone levels in Q4 were associated with lower odds of current wheeze in men (aOR for Q4 versus Q1=0.86, 95% CI=0.77 to 0.95). Among women with asthma, free testosterone levels in Q4 were also associated with lower odds of ≥1 asthma hospitalisation. Among men, free testosterone was positively associated with FEV1 and FVC. Among women, free testosterone was negatively and weakly associated with FVC.ConclusionIn a large study of British adults, elevated free testosterone levels are associated with lower odds of asthma and current wheeze in women and men, lower odds of asthma hospitalisations in women, and higher FEV1 and FVC in men.Dissemination to participants, and related patient and public communitiesThe results of the study will be linked to the UK Biobank website.

show abstract

Section: Discussioncontrasting

confidence: 69%

Serum free testosterone and asthma, asthma hospitalisations and lung function in British adults

Han

Yan

Yang

et al. 2020

Thorax

View full text Add to dashboard Cite

show abstract

“…Moreover, in our study into PCa samples, a trend towards decreased CD163+ macrophage infiltration was observed in treated patients compared to untreated patients. Studies in mice also showed that androgens enhance TAM polarization in vivo and in vitro 59,60 . Moreover, alveolar macrophages lacking AR were shown to express less TAM markers as well as a lower chemokine production then ARproficient macrophages, supporting our findings 61 .…”

Section: Discussionmentioning

confidence: 94%

Androgen receptor signalling in macrophages promotes TREM-1-mediated prostate cancer cell line migration and invasion

et al. 2020

View full text Add to dashboard Cite

The androgen receptor (AR) is the master regulator of prostate cancer (PCa) development, and inhibition of AR signalling is the most effective PCa treatment. AR is expressed in PCa cells and also in the PCa-associated stroma, including infiltrating macrophages. Macrophages have a decisive function in PCa initiation and progression, but the role of AR in macrophages remains largely unexplored. Here, we show that AR signalling in the macrophage-like THP-1 cell line supports PCa cell line migration and invasion in culture via increased Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) signalling and expression of its downstream cytokines. Moreover, AR signalling in THP-1 and monocyte-derived macrophages upregulates IL-10 and markers of tissue residency. In conclusion, our data suggest that AR signalling in macrophages may support PCa invasiveness, and blocking this process may constitute one mechanism of anti-androgen therapy.

show abstract

“…Recently, we have shown that myeloid AR does not affect myeloid cell infiltration into subcutaneously implanted C2 prostate tumors, suggesting that AR does not affect blood monocytes tumor migration (18). Alveolar macrophages from MARKO male mice display decreased cytokine and chemokine production in a model of allergic lung inflammation, and these changes are associated with decreased eosinophil infiltration to lung (30). It still remains to be determined how AR is impacting monocyte subsets in models of infection and inflammation, and how decreased CM to NCM ratio impacts disease susceptibility and progression.…”

Section: Discussionmentioning

confidence: 99%

Androgen Receptor Signaling Positively Regulates Monocytic Development

Consiglio

Gollnick

2020

Front. Immunol.

View full text Add to dashboard Cite

Myeloid cells are critical cells involved in the orchestration of innate and adaptive immune responses. Most myeloid cells derive from the adult bone marrow in a process called myelopoiesis, a tightly controlled process that ensures constant production of myeloid cells. Sex differences in myeloid cell development have been observed; males exhibit greater monocytic differentiation in the bone marrow, and men have increased blood monocyte numbers when compared to women. Here we use a genetic mouse model of myeloid androgen receptor (AR) knockout (MARKO) and pharmacological inhibition of AR to investigate the role of androgen signaling in monocytic differentiation. We observe that although myeloid AR signaling does not influence total bone marrow cell numbers, it does affect the composition of the bone marrow myeloid population in both homeostatic and emergency settings. Genetic deletion of AR in myeloid cells led to reduced monocytic development in vivo. Similarly, pharmacologic inhibition of AR signaling in vitro reduced monocytic development. However, alteration in monocytic differentiation in the absence of AR signaling did not lead to reduced numbers of circulating myeloid cells, although MARKO male mice display reduced ratio of classical to non-classical monocytes in the blood, implying that blood monocyte subsets are skewed upon myeloid AR deletion. Our results suggest that the sex differences observed in monocytic differentiation are partly attributed to the positive role of the androgen-AR axis in regulating monocytic development directly at the myeloid cell level. Furthermore, we have identified a novel role for AR in regulating blood mature monocyte subset turnover. Investigating how androgen signaling affects monocytic development and monocyte subset heterogeneity will advance our understanding of sex differences in monocytic function at homeostasis and disease and can ultimately impact future therapeutic design targeting monocytes in the clinic.

show abstract

Androgen and Androgen Receptor as Enhancers of M2 Macrophage Polarization in Allergic Lung Inflammation

Cited by 115 publications

References 58 publications

Serum free testosterone and asthma, asthma hospitalisations and lung function in British adults

Serum free testosterone and asthma, asthma hospitalisations and lung function in British adults

Androgen receptor signalling in macrophages promotes TREM-1-mediated prostate cancer cell line migration and invasion

Androgen Receptor Signaling Positively Regulates Monocytic Development

Contact Info

Product

Resources

About