IL-7 induces type 2 cytokine response in lung ILC2s and regulates GATA3 and CD25 expression.

Interleukin-7 is a cytokine with well-established roles in lymphocyte development and more recently, an expanded role in immune function. IL-7Rα is highly expressed by innate lymphoid cells (ILCs), but how IL-7 directs the development or function of ILCs is not well studied. Using mice with inducible deletion of IL-7Rα, we showed that loss of IL-7 signaling led to impaired production of IL-5, IL-13 and amphiregulin in lung ST2+ group 2 innate lymphoid cells (ILC2s) following influenza/A infection. Conversely, mice treated with IL-7 increased production of IL-5 and IL-13 by lung ILC2s. Moreover, we showed that IL-7 enhanced GATA3 and CD25 expression in ILC2s and loss of IL-7 signaling led to their reduced expression. Altogether, this study demonstrates that IL-7 regulates the function of ILC2s during airway viral infection and induces GATA3 and CD25 expression.

Selective dependence on IL-7 for antigen-specific CD8 T cell responses during airway influenza infection.

Interleukin-7 (IL-7) is a cytokine known for its importance in T cell development and survival. How IL-7 shapes CD8 T cell responses during an acute viral infection is less understood. We had previously shown that IL-7 signaling deficient mice have reduced accumulation of influenza-specific CD8 T cells following influenza infection. We sought to determine whether IL-7 affects early CD8 T cell expansion in the mediastinal lymph node and effector function in the lungs. Using IL-7Rα signaling deficient mice, we show that IL-7 is required for a normal sized mediastinal lymph node and the early clonal expansion of influenza-specific CD8 T cells therein. We show that IL-7 plays a cell-intrinsic role in the accumulation of NP366-374 and PA224-233-specific CD8 T cells in the lymph node. We also found that IL-7 shapes terminal differentiation, degranulation and cytokine production to a greater extent in PA224-233-specific than NP366-374-specific CD8 T cells. We further demonstrate that IL-7 is induced in the lung tissue by viral infection and we characterize multiple cellular sources that contribute to IL-7 production. Our findings on IL-7 and its effects on lower respiratory diseases will be important for expanding the utility of therapeutics that are currently available.

Interleukin-7 Receptor Alpha in Innate Lymphoid Cells: More Than a Marker.

Innate lymphoid cells (ILCs) are a group of immune cells that are important for defense against pathogens, tissue repair, and lymphoid organogenesis. They share similar characteristics with various subsets of helper T cells but lack specific antigen receptors. Interleukin-7 (IL-7) and thymic stromal lymphopoietin (TSLP) are cytokines that engage the IL-7Rα and have major roles in dictating the fate of ILCs. Recent advances in the field have revealed transcriptional programs associated with ILC development and function. In this article, we will review recent studies of the role of IL-7 and TSLP in ILC development and function during infection and inflammation.

Interleukin-7 in the transition of bone marrow progenitors to the thymus.

Interleukin-7 (IL-7) is essential for the development of T cells in humans and mice where deficiencies in IL-7 signaling result in severe immunodeficiency. T cells require IL-7 at multiple points during development; however, it is unclear when IL-7 is first necessary. We observed that mice with impaired IL-7 signaling had a large reduction in the number of early thymic progenitors (ETPs) while mice that overexpress IL-7 had greatly increased numbers of ETPs. These results indicated that the development of ETPs is sensitive to IL-7. Bone marrow progenitors of ETP are present in normal numbers in mice with impaired IL-7 signaling (IL-7Rα449F) and were efficiently recruited to the thymus. Furthermore, ETPs and their progenitors from IL-7Rα449F mice did not undergo increased apoptosis and proliferate normally compared to WT cells. Mixed bone marrow chimeras demonstrated that IL-7 signaling has a cell-intrinsic role in ETP development but was not required for development of bone marrow progenitors. We have shown a novel role for IL-7 signaling in the development of ETPs that is distinct from classic mechanisms of IL-7 regulating survival and proliferation.

Interleukin-3-deficient mice have increased resistance to blood-stage malaria.

The contribution of interleukin-3 (IL-3), a hematopoietic growth factor and immunoregulatory cytokine, to resistance to blood-stage malaria was investigated by infecting IL-3-deficient (knockout [KO]) mice with Plasmodium berghei NK65. Male IL-3 KO mice, but not female mice, were more resistant to infection than wild-type (WT) mice, as evidenced by lower peak parasitemia and prolonged survival. Both male and female IL-3 KO mice had increased splenomegaly and were more anemic than corresponding WT mice. Anemia was compensated for by an increase in bone marrow and splenic erythropoiesis in IL-3 KO mice, as evidenced by higher levels of erythroid progenitors. Plasma levels of gamma interferon (IFN-γ) and CXCL9 (monokine induced by IFN-γ [MIG]) were found to be significantly reduced in IL-3 KO mice during early stages of infection. In contrast, granulocyte colony-stimulating factor (G-CSF) levels were significantly higher, and the percentage of peripheral blood neutrophils lower, in infected IL-3 KO mice than in WT counterparts. Overall, our results indicate that IL-3 plays a critical role in suppressing protective immunity to P. berghei NK65 infection and that it is involved in inhibiting the development of splenomegaly, anemia, and erythropoiesis. IL-3 also influences IFN-γ, CXCL9, and G-CSF production in response to infection. The abnormal responses seen in infected IL-3 KO mice may be due to the lack of IL-3 during development, to the lack of IL-3 in the infected mature mice, or to both.

Home caregivers' satisfaction with the services provided by Riyadh Military Hospital's home support program.

BACKGROUND AND OBJECTIVES: The satisfaction of the family is essential to the success of home care support services. This study aimed to assess home caregivers' satisfaction with support services and to identify potential factors affecting their satisfaction. DESIGN AND SETTINGS: The study was conducted in the Family and Community Medicine Department at Riyadh Military Hospital using cross-sectional design over a period of six months. PATIENTS AND METHODS: Two hundred forty participants were recruited by systematic random sampling from the division registry. Data were collected through telephone calls using a designed structured interview form. All research ethics principles were followed. RESULTS: The response rate was 76.25%. Most caregivers were patients' sons or daughters. The duration of patients' disabling illnesses varied from less than 1 year to up to 40 years. The majority of caregivers agreed that a home care services team provided the proper healthcare-related support to the patients and improved caregivers' self-confidence in caring for their patients. Overall, on a scale of 100%, the median level of satisfaction was 90%, and 73.2% of caregivers had a satisfaction score of 75% or higher. Increased age, female gender, and more frequent home visits were positive independent factors associated with caregivers' satisfaction scores. CONCLUSION: Although most caregivers are satisfied with the services provided by a home care support program, there are still areas of deficiency, particularly in physiotherapy, vocational therapy, and social services. The implications are that caregivers need to be educated and trained in caring for their patients and need to gain self-confidence in their skills. The program's administration should improve physiotherapy, vocational therapy, social services, and procedures for hospital referral.