Medullary thymic epithelial NF-kB-inducing kinase (NIK)/IKKα pathway shapes autoimmunity and liver and lung homeostasis in mice.

Aberrant T cell development is a pivotal risk factor for autoimmune disease; however, the underlying molecular mechanism of T cell overactivation is poorly understood. Here, we identified NF-κB-inducing kinase (NIK) and IkB kinase α (IKKα) in thymic epithelial cells (TECs) as essential regulators of T cell development. Mouse TEC-specific ablation of either NIK or IKKα resulted in severe T cell-mediated inflammation, injury, and fibrosis in the liver and lung, leading to premature death within 18 d of age. NIK or IKKα deficiency abrogated medullary TEC development, and led to breakdown of central tolerance, production of autoreactive T cells, and fatal autoimmune destruction in the liver and lung. TEC-specific ablation of NIK or IKKα also impaired thymic T cell development from the double-negative through the double-positive stages and inhibited peripheral B cell development. These results unravel a hitherto unrecognized essential role of TEC-intrinsic NIK and IKKα pathways in autoimmunity and T cell-instigated chronic liver and lung diseases.

Differences in spending for diabetes and multiple chronic conditions in Michigan Medicare beneficiaries.

OBJECTIVES: To determine which combinations of type 2 diabetes (T2D) and multiple chronic conditions (MCC) contribute to total spending and differences in spending between groups based on sex, race/ethnicity, and rural residency. STUDY DESIGN: Retrospective cohort study using 2012 Medicare claims data from beneficiaries in Michigan with T2D. METHODS: Zero-inflated Poisson regression models to estimate relationships of demographic characteristics and MCC combinations on hospital outpatient, acute inpatient, skilled nursing, hospice, and Part D drug spending. RESULTS: Across most MCC combinations, there are lower odds of no spending, with a concurrent increase in the expected mean of actual spending when payments are made, except for hospital outpatient costs. For hospital outpatient services, we observed lower spending across all MCC combinations. When controlling for MCC, we generally found that compared with White beneficiaries, Black, Asian/Pacific Islander, and Hispanic beneficiaries experience increased odds of no spending, but when payments were made, payments generally increased. American Indian/Alaska Native beneficiaries are the exception; they experience decreased odds of no payments for hospital outpatient and acute inpatient services, with a concurrent decrease in mean expected payments. CONCLUSIONS: When considering a range of MCC combinations, we observed differences in total payments between racial/ethnic minority groups and White beneficiaries. Our results highlight the ongoing need to make changes in the health care system to make the system more accessible to racial/ethnic minority groups.