Service provision conditions for foreign residents in municipalities in Japan.

Objectives: This study examined the actual conditions of service provision to foreign residents (FRs) addressing prevention of lifestyle-related diseases (LRDs) and disaster preparedness/disaster responses (DPRs) in Japanese municipalities. Materials and Methods: A cross-sectional study was performed using a self-administered questionnaire with representatives of public health nurses in each municipality in Japan from December 2021 to January 2022. Results: Services considering FRs are more likely to be implemented in cities than in towns, and in municipalities where FRs account for ≥2.2% of the population (proportion of FRs in the Japanese population at the time of the study) than in those with fewer FRs. Cities have larger populations and greater financial resources than towns. Factors associated with the implementation of services and measures necessary for providing services to FRs were the classification of the municipality as a city, a high percentage of FRs, and large variation in corresponding nationalities/countries of origin. Conclusions: Cross-disciplinary efforts and collaborations need to be strengthened to share available resources within local governments and experiences in providing services for FRs in other divisions/sections, rather than considering only how to provide services for FRs in the public health division/section.

Access to Health-Related Information, Health Services, and Welfare Services among South and Southeast Asian Immigrants in Japan: A Qualitative Study.

Migrants face several challenges in their daily lives in the host country due to limited knowledge about the language, culture, and social system of the host country. Their vulnerability increases in a time of crisis. During the COVID-19 pandemic, migrant communities were severely affected. Evidence on migrants' access to COVID-19-related information and services is limited. We conducted a qualitative, descriptive study among migrants from Vietnam, Myanmar, and Nepal living in Japan to explore the barriers and promoting factors for their access to health-related information, health services, and welfare services during the first wave of COVID-19. We used a thematic analysis to identify key themes according to the study's objectives. Further, these themes were assessed using an adapted version of the ecological model. The migrants mainly relied on the information available on social networking sites and were not aware of formal sources of information. Language was a major barrier, followed by cognitive bottlenecks and time constraints for migrants accessing health-related information and services. Social media, short-form information provided using their native language or plain Japanese and illustrations, and supportive people around could help them to access health-related information and services. The findings from this study demonstrate how migrants can represent a vulnerable group in a host country, even more so in a time of crisis.

Effect of EGLN1 Genetic Polymorphisms on Hemoglobin Concentration in Andean Highlanders.

The physiological characteristics of Andean natives living at high altitudes have been investigated extensively, with many studies reporting that Andean highlanders have a higher hemoglobin (Hb) concentration than other highlander populations. It has previously been reported that positive natural selection has acted independently on the egl-9 family hypoxia inducible factor 1 (EGLN1) gene in Tibetan and Andean highlanders and is related to Hb concentration in Tibetans. However, no study has yet revealed the genetic determinants of Hb concentration in Andeans even though several single-nucleotide polymorphisms (SNPs) in EGLN1 have previously been examined. Therefore, we explored the relationship between hematological measurements and tag SNPs designed to cover the whole EGLN1 genomic region in Andean highlanders living in Bolivia. Our findings indicated that haplotype frequencies estimated from the EGLN1 SNPs were significantly correlated with Hb concentration in the Bolivian highlanders. Moreover, we found that an Andean-dominant haplotype related to high Hb level may have expanded rapidly in ancestral Andean highlander populations. Analysis of genotype data in an ~436.3 kb genomic region containing EGLN1 using public databases indicated that the population structure based on EGLN1 genetic markers in Andean highlanders was largely different from that in other human populations. This finding may be related to an intrinsic or adaptive physiological characteristic of Andean highlanders. In conclusion, the high Hb concentrations in Andean highlanders can be partly characterized by EGLN1 genetic variants.

Individual variations and sex differences in hemodynamics with percutaneous arterial oxygen saturation (SpO2) in young Andean highlanders in Bolivia.

BACKGROUND: Many studies have reported specific adaptations to high altitude, but few studies have focused on physiological variations in high-altitude adaptation in Andean highlanders. This study aimed to investigate the relationships between SpO2 and related factors, including individual variations and sex differences, in Andean highlanders. METHODS: The participants were community-dwelling people in La Paz, Bolivia, aged 20 years and over (age range 20-34 years). A total of 50 men and 50 women participated in this study. Height, weight, SpO2, hemoglobin concentration, finger temperature, heart rate, and blood pressure were measured. Information about lifestyle was also obtained by interview. RESULTS: There were individual variations of SpO2 both in men (mean 89.9%, range 84.0-95.0%) and women (mean 91.0%, range 84.0-96.0%). On Student's t test, men had significantly lower heart rate (p = 0.046) and SpO2 (p = 0.030) than women. On the other hand, men had significantly higher SBP (p < 0.001), hemoglobin (p < 0.001), and finger temperature (p = 0.004). In men, multiple stepwise regression analysis showed that a higher SpO2 was correlated with a lower heart rate (ß = - 0.089, p = 0.007) and a higher finger temperature (ß = 0.308, p = 0.030) (r2 for model = 0.18). In women, a higher SpO2 was significantly correlated with a higher finger temperature (ß = 0.391, p = 0.015) (r2 for model = 0.12). A higher SpO2 was related to a higher finger temperature (ß = 0.286, p = 0.014) and a lower heart rate (ß = - 0.052, p = 0.029) in all participants (r2 for model = 0.21). Residual analysis showed that individual SpO2 values were randomly plotted. CONCLUSION: Random plots of SpO2 on residual analysis indicated that these variations were random error, such as biological variation. A higher SpO2 was related to a lower heart rate and finger temperature in men, but a higher SpO2 was related to finger temperature in women. These results suggest that there are individual variations and sex differences in the hemodynamic responses of high-altitude adaptation in Andean highlanders.

Factors associated with the awareness of contraceptive methods, understanding the prevention of HIV/AIDS and the perception of HIV/AIDS risk among secondary school students in Dar es Salaam, Tanzania.

Objective: To assess the awareness of contraceptive methods, understanding of HIV/AIDS prevention and the perception of HIV/AIDS risks among secondary school students in Tanzania. Methods: An anonymous self-administered questionnaire survey was conducted among secondary school students in Tanzania. The questionnaire included sociodemographic characteristics, awareness of contraceptive methods, an understanding of HIV/AIDS prevention, and the perception of HIV/AIDS risks. Three secondary schools were selected by considering the gender balance and location, which included the urban and surrounding areas. The research objectives, methods, and ethical considerations were explained, and the students voluntarily completed the questionnaire. Results: A total of 233 responses were collected, and 204 responses were considered valid for the analysis. The mean and standard deviation of age were 18.5 ± 1.0. Regardless of the gender, age, religion, and major course of study, the maternal educational status (adjusted odds ratio [AOR]: 3.129; 95% confidence interval [CI]: 1.324, 7.398; P=0.009) and the number of information sources (AOR: 7.023, 95% CI: 3.166, 15.579, P<0.001) demonstrated associations with the awareness of contraceptive methods. Respondents who lived outside a dormitory (AOR: 3.782; 95% CI: 1.650, 8.671; P=0.002) and who currently had a partner (AOR: 3.616; 95% CI: 1.486, 8.800; P=0.005) were associated with a high level of understanding of HIV/AIDS prevention regardless of gender, age, religion, and major course of study. Respondents with few information sources were associated with a high level of perception of HIV/AIDS risks (AOR: 0.293; 95% CI: 0.115, 0.747; P=0.010), regardless of gender, age, religion, and major course of study. Conclusion: Factors associated with the awareness of contraceptive methods, the understanding of HIV/AIDS prevention, and perception of HIV/AIDS risks were not consistent. To ensure the improvement of these factors among secondary school students, sexual health education should be integrated into educational programs and provided holistically.

Experiences of romantic relationships and desires to marry and have children among youth in a low-fertility society.

Introduction: This study aims to explore experiences of romantic relationships and to examine determinants of desires to marry and have children in the future among Japanese university students. Methods: A cross-sectional study was conducted among undergraduate students of A University, located in the capital city of a Japanese prefecture, using an anonymous self-administered and structured questionnaire developed by an online survey software. Results: A total of 815 respondents with complete data were analyzed by logistic regression analysis. Over 80% of males and females expressed the desire to marry and have children in the future. It was found that for both female and male respondents, the "desire to marry" was associated with currently being in a romantic relationship or having experience of sexual intercourse. On the contrary, the "desire to have children" was associated with currently being in a romantic relationship or having experience of sexual intercourse only among male respondents, and no significant association was observed among female respondents. Conclusion: "Currently being in a romantic relationship" and "having experience of sexual intercourse" were associated with wanting to marry and have children in the future among male university students. This suggests that these may be important factors in providing a positive perception regarding having children when they attain childbearing age.

Factors associated with social support in child-rearing among mothers in post-disaster communities.

BACKGROUND: Natural disasters have long-term negative impacts on the health and socioenvironmental conditions of a population, affecting the physical environment as well as the relationships within the community, including social networks. Mothers in post-disaster communities may have difficulty receiving social support not only from family members and relatives but also from members of their community, such as people in their neighborhoods. This study focused on mothers with infants and preschool-aged children in post-disaster communities. The associations of social support with sociodemographic characteristics and socioenvironmental conditions related to child-rearing among mothers in post-disaster communities were assessed. METHODS: An anonymous self-administered questionnaire survey was conducted in October 2015 in 988 households in areas affected by the Great East Japan Earthquake and Tsunami. The data collected on sociodemographic and socioenvironmental characteristics included the presence of pre-disaster acquaintances in the neighborhood and social support for child-rearing. The associations of sociodemographic and socioenvironmental characteristics with social support were examined. RESULTS: We analyzed 215 completed questionnaires from mothers living in different houses from those they lived in before the disaster to reflect continuous relationships with people from the pre-disaster communities. Social support was significantly associated with infant sex, extended family, support obtained from relatives not living together, pre-disaster acquaintances, use of child support resources, and no perceived difficulties in child-rearing. In addition, the presence of pre-disaster acquaintances was associated with categories of mental/physical place of comfort and child-rearing support, with adjusted odds ratios of 1.88 (95% CI 1.03-3.44) and 2.84 (95% CI 1.46-5.52) compared with mothers who did not have any pre-disaster acquaintances. CONCLUSIONS: Factors associated with the obtainment of social support in child-rearing among mothers in post-disaster communities were attributed not only to mothers themselves and family members but also to socioenvironmental factors such as the presence of pre-disaster acquaintances. The presence of pre-disaster acquaintances promoted rich social support in child-rearing in post-disaster communities. When reconstructing a community following changes in residence location after a disaster, the pre-disaster relationships among the community dwellers should be considered from the viewpoint of child-rearing support.

Interest in medical health care for foreign residents among Japanese nursing students in areas of varying ethnic diversity.

BACKGROUND: Exposure of nursing students to foreign residents may improve cultural understanding. Nursing students are expected to have differing rates of contact with foreign residents, depending on how many foreign residents live in their municipality where they study in. Those in areas densely populated by foreign residents are more likely to encounter foreigners, and to have favorable views of them than students in areas with sparser foreign-resident populations. As of 2015, 2.23 million foreign residents lived in Japan, equaling 1.76% of the population; however, Japan still has fewer foreign-born residents compared to other countries. Therefore, interest in Medical Health Care for Foreign Residents (MHCFR) may be greater in students in ethnically diverse areas. While nursing students may have different levels of recognition of foreign nationals as potential clients and interest in MHCFR, no research validates this assumption. OBJECTIVES: This study aimed to clarify the association between proximity to foreign nationals and interest in MHCFR among Japanese nursing students. The secondary purpose was to describe knowledge and interest regarding MHCFR among students. To elucidate these topics, education and development of human resources in MHCFR should be considered. RESEARCH DESIGN AND METHOD: The study design was cross-sectional. A self-administered questionnaire survey was conducted with 143 nursing students. RESULTS: Most students understood the likelihood of providing nursing care to foreigners; however, knowledge and interest were low, regardless of whether lectures on MHCFR were provided. Knowledge of MHCFR, recognition of providing care to foreign nationals, and level of contact experiences with foreign nationals were significantly associated with students' level of interest in MHCFR. DISCUSSION: Nursing students in ethnically diverse areas tend to show greater interest in MHCFR in Japan. To foster global health perspectives, including MHCFR, in nursing students studying in ethnically diverse areas, contact experiences with foreigners and acceptance of international students by universities might be effective.

Associations among anthropometric measures, food consumption, and quality of life in school-age children in Tanzania.

Objectives: The factors associated with quality of life (QOL) and anthropometric measurements as outcomes of food consumption were examined among school-age children in Tanzania. Methods: A cross-sectional study was undertaken in September 2013 in Tanzania. Anonymous self-administered questionnaire surveys were conducted in the Kiswahili language among primary school children in the fifth and/or sixth grade aged 10-14 years. The survey probed sociodemographic characteristics such as age, gender, living with family members, number of meals/snacks per day, food consumption in the previous 24 hours, and QOL, as well as anthropometric measurements (height and weight). The Rohrer index was calculated based on height and weight. After presenting the mean and standard deviation (SD) of height, weight, and the Rohrer index score by age and gender, the Rohrer index score was categorized into three groups (low weight, normal weight, and overweight) and analyzed according to sociodemographic characteristics and food consumption using the chi-square test. Furthermore, the QOL score was analyzed using the t test. Multivariate linear regression analysis was used to analyze the associations between the QOL score and sociodemographic characteristics and food consumption. Results: A total of 694 children (male: 312; female: 382) participated in this study. According to the Rohrer index, 273 (39.3%) children were classified as low weight, 353 (50.9%) were normal weight, and 68 (9.8%) were overweight. A total of 459 (66.1%) children reported having had three or more meals and/or snacks on the day before the study. In addition, 127 (18.3%) children had not eaten any protein-rich food on the day before the study, although almost all had eaten at least one carbohydrate-rich food per day. Regardless of region, location, gender, and age, living without parents was associated with short stature (P = 0.010). A high QOL score was associated with having three or more meals and/or snacks per day (P < 0.001). Conclusions: The security of physiological needs such as a guarantee of three meals per day could contribute to higher QOL among underserved children.

Enhanced transgene expression by plasmid-specific recruitment of histone acetyltransferase.

Histone acetylation is associated with the activation of genes on chromosomes. Transgene expression from plasmid DNA might be increased by the acetylation of histones bound to plasmid DNA. To examine this hypothesis, we employed a positive feedback system, using a fusion protein of the sequence-specific DNA binding domain of yeast GAL4 and the histone acetyltransferase (HAT) domain of mouse CREB-binding protein (GAL4-HAT), in which GAL4-HAT promotes its own expression as well as that of a reporter gene product (luciferase). The activator plasmid DNA carrying the gene encoding GAL4-HAT was introduced into mouse Hepa1-6 cells, together with the reporter plasmid DNA, by lipofection. Significantly increased luciferase expression was observed by the co-introduction of the activator plasmid DNA. Moreover, the acetylation of histones bound to the reporter plasmid DNA was enriched by the activator plasmid DNA. These results indicated that the GAL4-HAT system is useful for enhanced transgene expression.

Chemical synthesis of erythropoietin glycoforms for insights into the relationship between glycosylation pattern and bioactivity.

The role of sialyloligosaccharides on the surface of secreted glycoproteins is still unclear because of the difficulty in the preparation of sialylglycoproteins in a homogeneous form. We selected erythropoietin (EPO) as a target molecule and designed an efficient synthetic strategy for the chemical synthesis of a homogeneous form of five EPO glycoforms varying in glycosylation position and the number of human-type biantennary sialyloligosaccharides. A segment coupling strategy performed by native chemical ligation using six peptide segments including glycopeptides yielded homogeneous EPO glycopeptides, and folding experiments of these glycopeptides afforded the correctly folded EPO glycoforms. In an in vivo erythropoiesis assay in mice, all of the EPO glycoforms displayed biological activity, in particular the EPO bearing three sialyloligosaccharides, which exhibited the highest activity. Furthermore, we observed that the hydrophilicity and biological activity of the EPO glycoforms varied depending on the glycosylation pattern. This knowledge will pave the way for the development of homogeneous biologics by chemical synthesis.

Reactions of community members regarding community health workers' activities as a measure of the impact of a training program in Amazonas, Brazil.

OBJECTIVES: The aim of this study was to evaluate the impact of community health worker (CHW) training on recognition and satisfaction regarding the performance of CHWs among members of the community in Amazonas, Brazil, which is a resource-poor area underserved with regard to medical health-care accessibility. METHODS: Baseline and endline surveys concerning recognition and satisfaction with respect to CHW performance among members of the community were conducted by interview using a questionnaire before and after implementation of a program to strengthen community health projects in Manicoré, Amazonas, Brazil. One of the components of the project was CHW refresher training, which focused on facilitating adequate use of health-care services and providing primary health care, including health guidance. The baseline survey was performed in February 2004 at the beginning of the project, and the endline survey was performed in February 2006 at the end of the project. There were 82 and 120 CHWs working in Manicoré at the times of the baseline and endline surveys, respectively. Statistical analysis was performed to determine the significance of changes in experience with CHW activities, expected functions of CHWs, and satisfaction regarding the performance of CHWs between the baseline and endline surveys. In addition, qualitative analysis was conducted to evaluate the acceptability, feasibility, and sustainability of CHW refresher training. RESULTS: Overall recognition and level of satisfaction regarding CHW performance among members of the community were improved from the baseline to the endline survey, regardless of type of residential area, such as town and/or remote area. Members of the community came to not expect CHWs to "provide strong medicine" (P < 0.001) and "provide injections" (P < 0.001), and came to appreciate "go to hospital with a sick person" (P = 0.031) as a function and role of CHWs. CONCLUSIONS: The results of the present study indicated that steady approaches to motivate and support CHWs in resource-limited settings could improve performance of CHWs and satisfaction of people in the community regarding the activities of CHWs to sustain their health.

Efficient synthesis of polypeptide-α-thioester by the method combining polypeptide expression and chemical activation for the semi-synthesis of interferon-γ having oligosaccharides.

In order to synthesize interferon-γ glycoform having an oligosaccharide at the 97 position by a semi-synthetic method, interferon-γ-polypeptide-(1-94)-α-hydrazide was prepared by the specific Cys-cyanylation of polypeptide-(1-94)-Cys-His6 expressed from E. coli and subsequent hydrazinolysis in 22% yield (two steps). This polypeptide-α-hydrazide was then converted into corresponding polypeptide-α-thioester under NaNO2 /acid conditions followed by thiolysis in 83% yield.

Chemical synthesis of a synthetic analogue of the sialic acid-binding lectin siglec-7.

As a basis for the development of an artificial carbohydrate-binding lectin, we chemically synthesized a domain of siglec-7, a well-characterized sialic-acid-binding lectin. The full polypeptide (127 amino acids) was constructed by sequential native chemical ligation (NCL) of five peptide segments. Because of poor cysteine availability for NCL, cysteine residues were introduced at suitable ligation sites; these cysteine residues were alkylated in order to mimic native glutamine or asparagine residues, or converted to an alanine residue by desulfurization after NCL. After folding the full-length polypeptide, the sialic-acid-binding activity of the synthetic siglec-7 was clearly demonstrated by STD NMR and ELISA experiments. We succeeded in the synthesis of siglec-7 by installing three extra cysteine residues with side-chain modifications and found that these modifications did not affect the binding activity.

RhoA/Rho kinase signaling in the cumulus mediates extracellular matrix assembly.

Cumulus cells surround the oocyte and regulate the production and assembly of the extracellular matrix (ECM) around the cumulus-oocyte complex for its timely interaction with sperm in the oviduct. We recently found that C-C chemokines such as CCL2, CCL7, and CCL9 are produced and stimulate integrin-mediated ECM assembly in the postovulatory cumulus to protect eggs and that prostaglandin E(2)-EP2 signaling in the cumulus cells facilitates fertilization by suppressing this chemokine signaling, which otherwise results in fertilization failure by preventing sperm penetration through the cumulus ECM. However, it remains unknown as to what mechanisms underlie chemokine-induced cumulus ECM assembly. Here we report that inhibition of EP2 signaling or addition of CCL7 augments RhoA activation and induces the surface accumulation of integrin and the contraction of cumulus cells. Enhanced surface accumulation of integrin then stimulates the formation and assembly of fibronectin fibrils as well as induces cumulus ECM resistance to hyaluronidase and sperm penetration. These changes in the cumulus ECM as well as cell contraction are relieved by the addition of Y27632 or blebbistatin. These results suggest that chemokines induce integrin engagement to the ECM and consequent ECM remodeling through the RhoA/Rho kinase/actomyosin pathway, making the cumulus ECM barrier resistant to sperm penetration. Based on these results, we propose that prostaglandin E(2)-EP2 signaling negatively regulates chemokine-induced Rho/ROCK signaling in cumulus cells for successful fertilization.

IFN-gamma expression in CD8+ T cells regulated by IL-6 signal is involved in superantigen-mediated CD4+ T cell death.

Infection with pathogens containing superantigens (Sags) can result in massive excessive CD4+ T cell activation and death in such conditions as toxic shock, food poisoning and autoimmune diseases. We here showed how enhancement of IL-6 signaling suppresses Sag-mediated activated CD4+ T cell death. Sag-induced CD4+ T cell death increased in IL-6 knockout (KO) mice, whereas it decreased in mice characterized by enhanced IL-6-gp130-STAT3 signaling. The serum concentration of IFN-gamma was inversely correlated with the magnitude of IL-6 signaling, and IFN-gamma deficiency inhibited Sag-induced activated CD4+ T cell death, suggesting that IL-6 suppresses CD4+ T cell death via IFN-gamma expression. Interestingly, depletion of activated CD8+ T cells inhibited Sag-mediated increases in IFN-gamma expression in IL-6 KO mice as well as the augmented CD4+ T cell death. The results demonstrate that IL-6-gp130-STAT3 signaling in activated CD8+ T cells contributes to Sag-induced CD4+ T cell death via IFN-gamma expression, highlighting this signaling axis in CD8+ T cells as a potential therapeutic target for Sag-related syndromes.

Interleukin-17 promotes autoimmunity by triggering a positive-feedback loop via interleukin-6 induction.

Dysregulated cytokine expression and signaling are major contributors to a number of autoimmune diseases. Interleukin-17A (IL-17A) and IL-6 are important in many disorders characterized by immune self-recognition, and IL-6 is known to induce the differentiation of T helper 17 (Th17) cells. Here we described an IL-17A-triggered positive-feedback loop of IL-6 signaling, which involved the activation of the transcription factors nuclear factor (NF)-kappaB and signal transducer and activator of transcription 3 (STAT3) in fibroblasts. Importantly, enhancement of this loop caused by disruption of suppressor of cytokine signaling 3 (SOCS3)-dependent negative regulation of the IL-6 signal transducer gp130 contributed to the development of arthritis. Because this mechanism also enhanced experimental autoimmune encephalomyelitis (EAE) in wild-type mice, it may be a general etiologic process underlying other Th17 cell-mediated autoimmune diseases.

IL-6-gp130-STAT3 in T cells directs the development of IL-17+ Th with a minimum effect on that of Treg in the steady state.

IL-17-producing Th (Th17) comprise a distinct lineage of pro-inflammatory Th that are major contributors to autoimmune diseases. Treatment with IL-6 and transforming growth factor beta (TGFbeta) induces naive CD4+ T cells to generate Th17, which also requires expression of the IL-6/TGFbeta target RORgammat. We reported that IL-6 transduces two signaling pathways via tyrosine redidues of the signal transducer gp130: one depends on signal transducers and activators of transcription (STAT)-3 activation and the other on Src homology region 2 domain-containing phosphatase 2 (SHP2)/Grb2 associated binder (Gab)/mitogen-activated protein kinase (MAPK) activation. Here, we showed that CD4+ T cells carrying a mutant gp130 that transduces the SHP2/Gab/MAPK pathway but not the STAT3-mediated one failed to develop into Th17, while CD4+ T cells whose mutant gp130 transduces the STAT3 signal only generated Th17, indicating that IL-6 acts directly on T cells through the tyrosine residues of gp130 required for STAT3 activation to promote the development of Th17. Moreover, we found that gp130-STAT3 pathway is essential for Th17 development and for the expression of RORgammat by using T cells specifically lacking gp130 and STAT3. Noteworthy is that the regulatory T cell (Treg) percentages and numbers were comparable between all mutant mice we tested in vivo, although we showed that IL-6-gp130-STAT3 pathway suppressed Treg development in vitro. Thus, we conclude that IL-6 acts directly to promote the development of Th17 by activating the T cell gp130-STAT3 pathway but has a minimum effect on Treg development at least in the steady state in vivo. Therefore, blockade of IL-6-gp130-STAT3 pathway in CD4+ T cells could be a good target for controlling unwanted Th17-mediated immune responses including autoimmune diseases.

Autoimmune arthritis associated with mutated interleukin (IL)-6 receptor gp130 is driven by STAT3/IL-7-dependent homeostatic proliferation of CD4+ T cells.

Mice homozygous for the F759 mutation in the gp130 interleukin (IL)-6 receptor subunit have enhanced gp130-mediated signal transducer and activator of transcription (STAT)3 activation and spontaneously developed a lymphocyte-mediated rheumatoid arthritis-like joint disease. Here, we show that the development of the disease is dependent on both major histocompatibility complex (MHC) II-restricted CD4+ T cells and IL-6 family cytokines. In spite of the necessity for CD4+ T cells, the gp130 mutation was only required in nonhemtopoietic cells for the disease. The gp130 mutation resulted in enhanced production of IL-7. Conditional knockout of STAT3 in nonlymphoid cells showed that the enhancement of IL-7 production was dependent on STAT3 activation by IL-6 family cytokines. Homeostatic proliferation of CD4+ T cells was enhanced in gp130 mutant mice and acceleration of homeostatic proliferation enhanced the disease, whereas the inhibition of homeostatic proliferation suppressed the disease. Anti-IL-7 antibody treatment inhibited not only the enhanced homeostatic proliferation, but also the disease in gp130 mutant mice. Thus, our results show that autoimmune disease in gp130 mutant mice is caused by increased homeostatic proliferation of CD4+ T cells, which is due to elevated production of IL-7 by nonhematopoietic cells as a result of IL-6 family cytokine-gp130-STAT3 signaling.