RIPK1 plays a crucial role in maintaining regulatory T-Cell homeostasis by inhibiting both RIPK3- and FADD-mediated cell death.

Regulatory T (Treg) cells play an essential role in maintaining immune balance across various physiological and pathological conditions. However, the mechanisms underlying Treg homeostasis remain incompletely understood. Here, we report that RIPK1 is crucial for Treg cell survival and homeostasis. We generated mice with Treg cell-specific ablation of Ripk1 and found that these mice developed fatal systemic autoimmunity due to a dramatic reduction in the Treg cell compartment caused by excessive cell death. Unlike conventional T cells, Treg cells with Ripk1 deficiency were only partially rescued from cell death by blocking FADD-dependent apoptosis. However, simultaneous removal of both Fadd and Ripk3 completely restored the homeostasis of Ripk1-deficient Treg cells by blocking two cell death pathways. Thus, our study highlights the critical role of RIPK1 in regulating Treg cell homeostasis by controlling both apoptosis and necroptosis, thereby providing novel insights into the mechanisms of Treg cell homeostasis.

Excessive apoptosis of Rip1-deficient T cells leads to premature aging.

In mammals, the most remarkable T cell variations with aging are the shrinking of the naïve T cell pool and the enlargement of the memory T cell pool, which are partially caused by thymic involution. However, the mechanism underlying the relationship between T-cell changes and aging remains unclear. In this study, we find that T-cell-specific Rip1 KO mice show similar age-related T cell changes and exhibit signs of accelerated aging-like phenotypes, including inflammation, multiple age-related diseases, and a shorter lifespan. Mechanistically, Rip1-deficient T cells undergo excessive apoptosis and promote chronic inflammation. Consistent with this, blocking apoptosis by co-deletion of Fadd in Rip1-deficient T cells significantly rescues lymphopenia, the imbalance between naïve and memory T cells, and aging-like phenotypes, and prolongs life span in T-cell-specific Rip1 KO mice. These results suggest that the reduction and hyperactivation of T cells can have a significant impact on organismal health and lifespan, underscoring the importance of maintaining T cell homeostasis for healthy aging and prevention or treatment of age-related diseases.

Psychometric assessment of the Adherence to Asthma Medication Questionnaire in asthma patients in China: a validation study.

BACKGROUND: Patients' medication adherence plays a critical role in the treatment and rehabilitation of disease. However, few tools are currently available that can be used to identify the reasons for their nonadherence with their medication regimens. It is possible to evaluate both the level of medication adherence of a patient as well as the reasons for it using the Adherence to Asthma Medication Questionnaire (AAMQ). The purpose of this study was to adapt the AAMQ for use in Chinese patients and a variety of asthma patients. METHODS: A total of 242 asthma patients were recruited from Jinzhou in China. The Adherence to Asthma Medication Questionnaire was translated and back-translated using the Brislin translation model. Test-retest reliability, internal consistency, and stability all play a large role in determining the reliability of a scale. Confirmatory factor analysis was used to examine the scale's construct validity, and expert consultation was used to verify the scale's content validity. Statistics were deemed significant at p < 0.05. RESULTS: The Cronbach's α value of the Chinese version of the AAMQ was 0.866, and the coefficient values for the three domains ranged between 0.702 and 0.798. The split-half reliability and stability values were 0.794 and 0.772, respectively. The content validity index of the scale (S-CVI) was 0.923, and the content validity index of the level of scale entry was 0.857-1.000. According to the confirmatory factor analysis, the chi-square degreed of freedom were 1.484, and the model fitting indices were all within normal limits. CONCLUSIONS: The AAMQ had good reliability and validity for asthmatic patients. The results of the scale's assessment can be used as a criterion for medication adherence among asthmatic patients and to understand the causes. This study provides a reference for solving the problem of medication adherence among asthma patients and implementing targeted nursing measures. PATIENT OR PUBLIC CONTRIBUTION: Gratitude is extended to all individuals collaborating in completing the survey and to the author.

Predictors of caregiver burden in patients with neurologic Wilson disease.

OBJECTIVES: Caregiver burden in neurologic Wilson disease (NWD) has received little attention. We investigated predictors of caregiver burden in Chinese NWD patients. METHODS: Participants in this retrospective study were NWD patients admitted to The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine from 1 August to 31 December 2019. Sociodemographic information was recorded for caregivers and NWD patients. Caregiver burden was evaluated using the Caregiver Burden Inventory (CBI). Cognitive impairment, functional problems, depression and anxiety were evaluated by professional interviewers. Path analysis was used to evaluate predictors of CBI scores. RESULTS: Sixty NWD patients were enrolled (mean age: 21.35 ± 4.89 years; mean NWD duration: 7.85 ± 3.11 years). The mean CBI score was 52.00 ± 17.16. Care duration had a significant direct effect on CBI score after controlling for confounders (r = 0.493). Cognitive impairment (r = -0.426), functional problems (r = 0.581), depression (r = 0.349) and anxiety (r = 0.317) had significant indirect effects on CBI score. CONCLUSION: Caregivers of NWD patients may experience a medium level of caregiver burden. NWD duration, cognitive impairment, functional problems, depression and anxiety in NWD patients may be useful predictors of caregiver burden.

Foxp1 is critical for the maintenance of regulatory T-cell homeostasis and suppressive function.

Regulatory T (Treg) cells play central roles in maintaining immune homeostasis and self-tolerance. However, the molecular mechanisms underlying Treg cell homeostasis and suppressive function are still not fully understood. Here, we report that the deletion of another P subfamily members of the forkhead box (Foxp) subfamily member Foxp1 in Treg cells led to increased numbers of activated Treg (aTreg) cells at the expense of quiescent Treg cells, and also resulted in impaired Treg suppressive function. Mice with Foxp1-deficient Treg cells developed spontaneous inflammatory disease with age; they also had more severe inflammatory disease in colitis and experimental autoimmune encephalomyelitis (EAE) models. Mechanistically, we found that Foxp1 bound to the conserved noncoding sequence 2 (CNS2) element of the Foxp3 locus and helped maintain Treg suppressive function by stabilizing the Foxp3 expression. Furthermore, we found that Foxp1 and Foxp3 coordinated the regulation of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression levels. Taken together, our study demonstrates that Foxp1 plays critical roles in both maintaining Treg cell quiescence during homeostasis and regulating Treg suppressive function.