PU.1 Is Required for Macrophage Polarization and the Development of Allergic Inflammation

Rational: Alternatively activated macrophages (AAM) play a pivotal role in Th2 immune response. Although it was well proven that the transcription factor PU.1 has an important role in regulating differentiation and maturation of macrophages as well as modulating neutrophilic lung inflammation during endotoxemia, the roles of PU.1 in AAM polarization and in the pathogenesis of asthmatic inflammation have not been investigated yet. We hypothesized that PU.1 plays a critical role in polarizing AAM and the development of allergic airway inflammation. Methods and Results: PU/ER(T)+/- mice are heterozygotes of conditional PU.1 knock-out mice carrying a single PU.1 locus fused to the modified estrogen (E) receptor (R) ligand binding domain that is responsive to tamoxifen. IL-4, a cytokine polarizing macrophages towards AAM, significantly increased expression of PU.1 in bone marrow derived macrophages (BMDMs), which was similar with STAT6 phosphorylation, suggesting PU.1 is associated with AAM polarization. Upon treatment of IL-4 for 24 hours, BMDMs from PU/ER(T)+/- mice, compared to that from wide type (WT) mice, displayed attenuated expression of AAM specific markers Ym-1 and Fizz-1 by both western blot and real-time PCR assay. To determine whether PU.1 is involved for asthma development, we established triple allergen (DRA: dust mite, ragweed and aspergillus) combined murine asthma model. After repeated airway challenge with DRA, mice with deficient PU.1 showed attenuated cellular infiltration and goblet cell hyperplasia, which are characteristics of airway inflammation and remodeling, that corresponded to lower expression of arginase-1, Ym-1 and Fizz-1 in lungs than that of WT mice. Conclusion: Our results indicate that functionally intact PU.1 is required for AAM polarization and contributes to the eosinophilic inflammation and airway remodeling, suggesting that PU.1 is important for the allergic Th2 immune response through maintaining an AAM-regulated microenvironment

Age heterogeneity.

Today, population aging is the main trend of population development. Home-based care is mainly adopted in Chinese society, and scholars have paid ample attention to the effect of intergenerational support on the mental health of older people. However, research conclusions differ. This study uses data from the 2018 China Health and Pension Tracking Survey (CHARLS), which we analyzed with STATA software to construct least squares regression and two-stage least squares regression models. The regression model included 6,647 respondents to investigate the mental health status of older people based on depression status. Intergenerational support was defined as economic support, emotional support, and daily care provided by the children of older people. We studied the impact of three aspects of intergenerational support on the mental health of the elderly. We performed a robustness test using the variable replacement and propensity score matching methods, and analyzed age, gender, and urban-rural heterogeneity. The results showed that economic support had no significant impact on the mental health of older people, while emotional support and daily care had a positive effect. The heterogeneity results indicated that the relationship between intergenerational support and mental health of older people differed significantly based on age, gender, and urban and rural areas. Therefore, children should raise their awareness of supporting their parents, pay attention to their parents’ mental health, and provide emotional support and daily care. Furthermore, community work improves family relations, creates a good social environment, and encourages young people to respect and be filial to older people. The government should improve the medical security system and old-age service system, and provide policy support to help the mental health of older people.</div

Conceptual framework of intergenerational support and mental health.

Conceptual framework of intergenerational support and mental health.</p

Gender heterogeneity.

Today, population aging is the main trend of population development. Home-based care is mainly adopted in Chinese society, and scholars have paid ample attention to the effect of intergenerational support on the mental health of older people. However, research conclusions differ. This study uses data from the 2018 China Health and Pension Tracking Survey (CHARLS), which we analyzed with STATA software to construct least squares regression and two-stage least squares regression models. The regression model included 6,647 respondents to investigate the mental health status of older people based on depression status. Intergenerational support was defined as economic support, emotional support, and daily care provided by the children of older people. We studied the impact of three aspects of intergenerational support on the mental health of the elderly. We performed a robustness test using the variable replacement and propensity score matching methods, and analyzed age, gender, and urban-rural heterogeneity. The results showed that economic support had no significant impact on the mental health of older people, while emotional support and daily care had a positive effect. The heterogeneity results indicated that the relationship between intergenerational support and mental health of older people differed significantly based on age, gender, and urban and rural areas. Therefore, children should raise their awareness of supporting their parents, pay attention to their parents’ mental health, and provide emotional support and daily care. Furthermore, community work improves family relations, creates a good social environment, and encourages young people to respect and be filial to older people. The government should improve the medical security system and old-age service system, and provide policy support to help the mental health of older people.</div

S2 File -

Today, population aging is the main trend of population development. Home-based care is mainly adopted in Chinese society, and scholars have paid ample attention to the effect of intergenerational support on the mental health of older people. However, research conclusions differ. This study uses data from the 2018 China Health and Pension Tracking Survey (CHARLS), which we analyzed with STATA software to construct least squares regression and two-stage least squares regression models. The regression model included 6,647 respondents to investigate the mental health status of older people based on depression status. Intergenerational support was defined as economic support, emotional support, and daily care provided by the children of older people. We studied the impact of three aspects of intergenerational support on the mental health of the elderly. We performed a robustness test using the variable replacement and propensity score matching methods, and analyzed age, gender, and urban-rural heterogeneity. The results showed that economic support had no significant impact on the mental health of older people, while emotional support and daily care had a positive effect. The heterogeneity results indicated that the relationship between intergenerational support and mental health of older people differed significantly based on age, gender, and urban and rural areas. Therefore, children should raise their awareness of supporting their parents, pay attention to their parents’ mental health, and provide emotional support and daily care. Furthermore, community work improves family relations, creates a good social environment, and encourages young people to respect and be filial to older people. The government should improve the medical security system and old-age service system, and provide policy support to help the mental health of older people.</div

Alternative variable method.

Today, population aging is the main trend of population development. Home-based care is mainly adopted in Chinese society, and scholars have paid ample attention to the effect of intergenerational support on the mental health of older people. However, research conclusions differ. This study uses data from the 2018 China Health and Pension Tracking Survey (CHARLS), which we analyzed with STATA software to construct least squares regression and two-stage least squares regression models. The regression model included 6,647 respondents to investigate the mental health status of older people based on depression status. Intergenerational support was defined as economic support, emotional support, and daily care provided by the children of older people. We studied the impact of three aspects of intergenerational support on the mental health of the elderly. We performed a robustness test using the variable replacement and propensity score matching methods, and analyzed age, gender, and urban-rural heterogeneity. The results showed that economic support had no significant impact on the mental health of older people, while emotional support and daily care had a positive effect. The heterogeneity results indicated that the relationship between intergenerational support and mental health of older people differed significantly based on age, gender, and urban and rural areas. Therefore, children should raise their awareness of supporting their parents, pay attention to their parents’ mental health, and provide emotional support and daily care. Furthermore, community work improves family relations, creates a good social environment, and encourages young people to respect and be filial to older people. The government should improve the medical security system and old-age service system, and provide policy support to help the mental health of older people.</div

Urban-rural heterogeneity.

Today, population aging is the main trend of population development. Home-based care is mainly adopted in Chinese society, and scholars have paid ample attention to the effect of intergenerational support on the mental health of older people. However, research conclusions differ. This study uses data from the 2018 China Health and Pension Tracking Survey (CHARLS), which we analyzed with STATA software to construct least squares regression and two-stage least squares regression models. The regression model included 6,647 respondents to investigate the mental health status of older people based on depression status. Intergenerational support was defined as economic support, emotional support, and daily care provided by the children of older people. We studied the impact of three aspects of intergenerational support on the mental health of the elderly. We performed a robustness test using the variable replacement and propensity score matching methods, and analyzed age, gender, and urban-rural heterogeneity. The results showed that economic support had no significant impact on the mental health of older people, while emotional support and daily care had a positive effect. The heterogeneity results indicated that the relationship between intergenerational support and mental health of older people differed significantly based on age, gender, and urban and rural areas. Therefore, children should raise their awareness of supporting their parents, pay attention to their parents’ mental health, and provide emotional support and daily care. Furthermore, community work improves family relations, creates a good social environment, and encourages young people to respect and be filial to older people. The government should improve the medical security system and old-age service system, and provide policy support to help the mental health of older people.</div

S2 Dataset -

Today, population aging is the main trend of population development. Home-based care is mainly adopted in Chinese society, and scholars have paid ample attention to the effect of intergenerational support on the mental health of older people. However, research conclusions differ. This study uses data from the 2018 China Health and Pension Tracking Survey (CHARLS), which we analyzed with STATA software to construct least squares regression and two-stage least squares regression models. The regression model included 6,647 respondents to investigate the mental health status of older people based on depression status. Intergenerational support was defined as economic support, emotional support, and daily care provided by the children of older people. We studied the impact of three aspects of intergenerational support on the mental health of the elderly. We performed a robustness test using the variable replacement and propensity score matching methods, and analyzed age, gender, and urban-rural heterogeneity. The results showed that economic support had no significant impact on the mental health of older people, while emotional support and daily care had a positive effect. The heterogeneity results indicated that the relationship between intergenerational support and mental health of older people differed significantly based on age, gender, and urban and rural areas. Therefore, children should raise their awareness of supporting their parents, pay attention to their parents’ mental health, and provide emotional support and daily care. Furthermore, community work improves family relations, creates a good social environment, and encourages young people to respect and be filial to older people. The government should improve the medical security system and old-age service system, and provide policy support to help the mental health of older people.</div

Descriptive statistics of variables.

Today, population aging is the main trend of population development. Home-based care is mainly adopted in Chinese society, and scholars have paid ample attention to the effect of intergenerational support on the mental health of older people. However, research conclusions differ. This study uses data from the 2018 China Health and Pension Tracking Survey (CHARLS), which we analyzed with STATA software to construct least squares regression and two-stage least squares regression models. The regression model included 6,647 respondents to investigate the mental health status of older people based on depression status. Intergenerational support was defined as economic support, emotional support, and daily care provided by the children of older people. We studied the impact of three aspects of intergenerational support on the mental health of the elderly. We performed a robustness test using the variable replacement and propensity score matching methods, and analyzed age, gender, and urban-rural heterogeneity. The results showed that economic support had no significant impact on the mental health of older people, while emotional support and daily care had a positive effect. The heterogeneity results indicated that the relationship between intergenerational support and mental health of older people differed significantly based on age, gender, and urban and rural areas. Therefore, children should raise their awareness of supporting their parents, pay attention to their parents’ mental health, and provide emotional support and daily care. Furthermore, community work improves family relations, creates a good social environment, and encourages young people to respect and be filial to older people. The government should improve the medical security system and old-age service system, and provide policy support to help the mental health of older people.</div

Intergenerational support and mental health.

Today, population aging is the main trend of population development. Home-based care is mainly adopted in Chinese society, and scholars have paid ample attention to the effect of intergenerational support on the mental health of older people. However, research conclusions differ. This study uses data from the 2018 China Health and Pension Tracking Survey (CHARLS), which we analyzed with STATA software to construct least squares regression and two-stage least squares regression models. The regression model included 6,647 respondents to investigate the mental health status of older people based on depression status. Intergenerational support was defined as economic support, emotional support, and daily care provided by the children of older people. We studied the impact of three aspects of intergenerational support on the mental health of the elderly. We performed a robustness test using the variable replacement and propensity score matching methods, and analyzed age, gender, and urban-rural heterogeneity. The results showed that economic support had no significant impact on the mental health of older people, while emotional support and daily care had a positive effect. The heterogeneity results indicated that the relationship between intergenerational support and mental health of older people differed significantly based on age, gender, and urban and rural areas. Therefore, children should raise their awareness of supporting their parents, pay attention to their parents’ mental health, and provide emotional support and daily care. Furthermore, community work improves family relations, creates a good social environment, and encourages young people to respect and be filial to older people. The government should improve the medical security system and old-age service system, and provide policy support to help the mental health of older people.</div