It has been proposed that an inability to control immunoinflammatory processes may be a critical factor in the pathogenesis of asthma. Specific subsets of CD4+ """"""""T regulatory"""""""" (TR) cells promote tolerance to allergens and inhibit airway responsiveness in animal models, and may exert these effects in part through the production of anti-inflammatory cytokines (IL-10, TGF-Beta). Although information in humans is scarce, TR cells appear to be present at the time of birth, but are functionally immature. Information derived from mouse models suggests that stimulation of cytokines such as IL-10 in early life may drive the production of functional TR cells. Considering that exposure to endotoxin, a potent stimulus for IL-10, in childhood is associated with reduced risk for atopic diseases and asthma, this suggests that the risk of developing allergic diseases and/or asthma in early childhood is determined by two interactive factors: first, the degree to which TR cell maturation is developed in early life; and second, the timing, nature, and quantity of environmental exposure to innate immune stimuli. To test this hypothesis, we propose to study an established and well-characterized birth cohort at increased risk for allergies and asthma on the basis of parental history. Retrospective (from stored specimens), cross-sectional, and prospective measurements of immune development will evaluate phenotypic and functional indicators of TR cells during infancy and early childhood in children with a variety of allergic cutaneous and respiratory tract disorders, including asthma. In addition, dust specimens will be collected from the home for quantitative measurement of LPS, peptidoglycan, and selected allergens. Finally, we will analyze the contributions of environmental factors (innate stimuli and allergen exposure) and immunologic development (TR cells and cytokine responses) to the development, resolution, severity, and/or perpetuation of wheezing and/or allergic phenotypes in infancy and early childhood. The proposed experiments will not only measure the development of TR cells and their relationship to wheezing phenotypes and/or childhood asthma, but will also help to define how stimulation of the innate immune system relates to maturation of TR cells.
| Liggett, Stephen B; Bochkov, Yury A; Pappas, Tressa et al. (2014) Genome sequences of rhinovirus C isolates from wisconsin pediatric respiratory studies. Genome Announc 2: |
| Liggett, Stephen B; Bochkov, Yury A; Pappas, Tressa et al. (2014) Genome sequences of rhinovirus B isolates from wisconsin pediatric respiratory studies. Genome Announc 2: |
| Liggett, Stephen B; Bochkov, Yury A; Pappas, Tressa et al. (2014) Genome sequences of rhinovirus a isolates from wisconsin pediatric respiratory studies. Genome Announc 2: |
| McMahon, Douglas F; Rajamanickam, Victoria; Salazar, Lisa et al. (2012) Do asthma symptoms lag behind cold symptoms in a viral illness? J Allergy Clin Immunol 130:990-1 |
| Singh, Anne Marie; Evans, Michael D; Gangnon, Ronald et al. (2010) Expression patterns of atopic eczema and respiratory illnesses in a high-risk birth cohort. J Allergy Clin Immunol 125:491-493.e4 |
| Olenec, Jaime P; Kim, Woo Kyung; Lee, Wai-Ming et al. (2010) Weekly monitoring of children with asthma for infections and illness during common cold seasons. J Allergy Clin Immunol 125:1001-1006.e1 |
| Gern, James E (2009) Rhinovirus and the initiation of asthma. Curr Opin Allergy Clin Immunol 9:73-8 |
| Bufford, J D; Reardon, C L; Li, Z et al. (2008) Effects of dog ownership in early childhood on immune development and atopic diseases. Clin Exp Allergy 38:1635-43 |
| Jartti, Tuomas; Burmeister, Kristjan A; Seroogy, Christine M et al. (2007) Association between CD4(+)CD25(high) T cells and atopy in children. J Allergy Clin Immunol 120:177-83 |
