Wiskott-Aldrich syndrome protein deficiency in innate immune cells leads to mucosal immune dysregulation and colitis in mice

BACKGROUND & AIMS: Immunodeficiency and autoimmune sequelae, including colitis, develop in patients and mice deficient in Wiskott-Aldrich Syndrome protein (WASP), a hematopoietic-specific intracellular signaling molecule that regulates the actin cytoskeleton. Development of colitis in WASP-deficient mice requires lymphocytes; transfer of T cells is sufficient to induce colitis in immunodeficient mice. We investigated the interactions between innate and adaptive immune cells in mucosal regulation during development of T-cell-mediated colitis in mice with WASP-deficient cells of the innate immune system. METHODS: Naïve and/or regulatory CD4(+) T cells were transferred from 129 SvEv mice into RAG-2 deficient (RAG-2 KO) mice or mice lacking WASP and RAG-2 (WRDKO). Animals were observed for the development of colitis; effector and regulatory functions of innate immune and T cells were analyzed with in vivo and in vitro assays. RESULTS: Transfer of unfractionated CD4(+) T cells induced severe colitis in WRDKO, but not RAG-2 KO, mice. Naïve wild-type T cells had higher levels of effector activity and regulatory T cells had reduced suppressive function when transferred into WRDKO mice compared to RAG-2 KO mice. Regulatory T-cell proliferation, generation, and maintenance of FoxP3 expression were reduced in WRDKO recipients, and associated with reduced numbers of CD103(+) tolerogenic dendritic cells and levels of interleukin (IL)-10. Administration of IL-10 prevented induction of colitis following transfer of T cells into WRDKO mice. CONCLUSIONS: Defective interactions between WASP-deficient innate immune cells and normal T cells disrupt mucosal regulation, potentially by altering the functions of tolerogenic dendritic cells, production of IL-10, and homeostasis of regulatory T cells

Smoke-Free Multiunit Housing Policy: Caretakers’ Perspectives on Economic and Personal Impacts

Objective: Multiunit housing (MUH) operators may be motivated to adopt smoke-free policies to achieve cost savings. MUH caretakers provide a unique perspective for understanding the implications of smoke-free policies because of their role in property maintenance. We examine MUH caretakers’ perceptions regarding the economic and personal impact of smoke-free policies at their properties. Methods: We conducted and analyzed qualitative interviews with 20 multiunit housing caretakers from two large property management companies in the southeastern United States that had implemented smoke-free policies. Results: For non-smoking units, caretakers reported shortened turnover times, in addition to reduction in the need for turnover supplies and capital replacements. Caretakers reported an improvement in their work environments due to reduced workload and exposure to secondhand and thirdhand smoke after implementation of smoke-free policies. Conclusion: The potential for cost savings exists for MUH operators who enact smoke-free policies because of decreased labor, supplies, and capital costs. Smoke-free policies may also improve the work environment of caretakers and other frontline MUH employees. These are important findings for MUH companies seeking to lower their operation costs and improve their employees’ working conditions, as well as for smoke-free advocates seeking to promote policy change