IL-1 regulates the IL-23 response to wheat gliadin, the etiologic agent of Celiac Disease

Celiac disease (CD) is an autoimmune disease prevalent in ~1% of the general population. CD is unique because both the major genetic (Human Leukocyte Antigen-DQ2/DQ8 alleles) and etiologic factors (dietary glutens) for susceptibility are known. While these alleles are responsible for the inappropriate T cell response that characterizes CD, they are not sufficient since most HLA-DQ2+/DQ8+ individuals exposed to glutens never develop disease. The reasons for this have not been explained; however our novel findings strongly advocate a role for interleukin-23 (IL-23) in the immunopathogenesis of CD. We demonstrate that wheat gliadin stimulates monocytes to produce significantly higher amounts of inflammatory cytokines IL-1b, IL-23, and tumor necrosis factor-a (TNFa) in CD patients compared to HLA-DQ2+ healthy individuals. Furthermore, we determine that IL-1 signalling is obligatory for production of IL-23, since IL-1b triggers IL-23 secretion in a dose-dependent manner and IL-1 receptor antagonist (IL-1ra) blocks IL-23 responses to gliadin. Our results suggest that gliadin activation of monocytes and the subsequent robust secretion of IL-1b and IL-23 initiate the immune response cascade that is manifest as CD, and reveal for the first time that the IL-1 system regulates production of IL-23. The discovery of IL-23 has highlighted the critical role of the innate immune response in autoimmunity and other inflammatory conditions. We anticipate that our novel findings will lead to the discovery of therapeutic targets for this disease and other inflammatory diseases mediated by IL-23

Ex-vivo expanded human NK cells express activating receptors that mediate cytotoxicity of allogeneic and autologous cancer cell lines by direct recognition and antibody directed cellular cytotoxicity

10.1186/1756-9966-29-134Journal of Experimental and Clinical Cancer Research29113

Influence of a walking aid on temporal and spatial parameters of gait in healthy adults

This is the post-print version of the final paper published in PM&R. The published article is available from the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright @ 2014 Elsevier B.V.Objective - To determine the effect of using a walking aid on temporal and spatial parameters of gait when used for balance versus support on the dominant and nondominant hand side. Design - Repeated measures observational study design. Setting - University gymnasium. Participants - Twenty-seven healthy male and female adults of mean ± standard deviation age 44.74 ± 10.00 years. Methods - Five walking conditions (C) were completed by all participants on the GAITRite pressure mat. Normal walking (C1), walking with a cane in the dominant hand (C2) and nondominant hand (C3) as if using for balance, walking with a cane in the dominant hand (C4) and nondominant hand (C5) while allowing approximately 10% of the body weight through the cane. Main Outcome Measurements - Temporal measurements (swing time, stance time, single limb support time, double limb support time) as percentage of a gait cycle and the base of support for the left and the right foot for all 5 walking conditions. Results - A significant difference (P < .001) was observed between C1, C2, and C3 in percentage swing time and percentage stance time of the ipsilateral side, and in percentage single limb support time of the contralateral side. The double limb support time was significantly different (P ≤ .04) for both ipsilateral and contralateral sides. Comparisons among C1, C4, and C5 demonstrated significance (P < .001) for all variables. Post hoc analysis showed significance between C1 and C4, and C1 and C5 for all variables except percentage stance time of the ipsilateral side and percentage single limb support of the contralateral side. Conclusions - In healthy adults, use of a cane for balance modifies swing and stance parameters of the ipsilateral side and does not affect the base of support formed by the feet. When used for support, the cane alters the swing and stance parameters, and also the base of support formed by the feet