Innate and adaptive immune responses in asthma (original) (raw)

• Bowen, H. et al. Control of cytokine gene transcription in TH1 and TH2 cells. Clin. Exp. Allergy 38, 1422–1431 (2008).
  CAS Google Scholar
• Das, J. et al. A critical role for NF-κB in GATA3 expression and TH2 differentiation in allergic airway inflammation. Nat. Immunol. 2, 45–50 (2001).
  CAS Google Scholar
• Alfvén, T. et al. Allergic diseases and atopic sensitization in children related to farming and anthroposophic lifestyle—the PARSIFAL study. Allergy 61, 414–421 (2006).
  Google Scholar
• Ege, M.J. et al. Exposure to environmental microorganisms and childhood asthma. N. Engl. J. Med. 364, 701–709 (2011).
  CAS Google Scholar
• Ege, M.J. et al. Not all farming environments protect against the development of asthma and wheeze in children. J. Allergy Clin. Immunol. 119, 1140–1147 (2007).
  Google Scholar
• Ege, M.J. et al. Prenatal exposure to a farm environment modifies atopic sensitization at birth. J. Allergy Clin. Immunol. 122, 407–412 (2008).
  Google Scholar
• Sallmann, E. et al. High-affinity IgE receptors on dendritic cells exacerbate TH2-dependent inflammation. J. Immunol. 187, 164–171 (2011).
  CAS Google Scholar
• Nelson, D.J. et al. Development of the airway intraepithelial dendritic cell network in the rat from class II major histocompatibility (Ia)-negative precursors: differential regulation of Ia expression at different levels of the respiratory tract. J. Exp. Med. 179, 203–212 (1994).
  CAS Google Scholar
• McWilliam, A.S., Nelson, D., Thomas, J.A. & Holt, P.G. Rapid dendritic cell recruitment is a hallmark of the acute inflammatory response at mucosal surfaces. J. Exp. Med. 179, 1331–1336 (1994).
  CAS Google Scholar
• Hammad, H. et al. Inflammatory dendritic cells–not basophils–are necessary and sufficient for induction of Th2 immunity to inhaled house dust mite a llergen. J. Exp. Med. 207, 2097–2111 (2010).
  CAS Google Scholar
• Paul, W.E. & Zhu, J. How are TH2-type immune responses initiated and amplified? Nat. Rev. Immunol. 10, 225–235 (2010).
  CAS Google Scholar
• van Panhuys, N. et al. Basophils are the major producers of IL-4 during primary helminth infection. J. Immunol. 186, 2719–2728 (2011).
  CAS Google Scholar
• Trompette, A. et al. Allergenicity resulting from functional mimicry of a Toll-like receptor complex protein. Nature 457, 585–588 (2009).
  CAS Google Scholar
• Lu, T.X. et al. MicroRNA-21 limits in vivo immune response-mediated activation of the IL-12/IFN-γ pathway, Th1 polarization, and the severity of delayed-type hypersensitivity. J. Immunol. 187, 3362–3373 (2011).
  CAS Google Scholar
• Simpson, A. et al. Beyond atopy: multiple patterns of sensitization in relation to asthma in a birth cohort study. Am. J. Respir. Crit. Care Med. 181, 1200–1206 (2010).
  Google Scholar
• Moffatt, M.F. et al. A large-scale, consortium-based genomewide association study of asthma. N. Engl. J. Med. 363, 1211–1221 (2010).
  CAS Google Scholar
• Granada, M. et al. A genome-wide association study of plasma total IgE concentrations in the Framingham Heart Study. J. Allergy Clin. Immunol. 129, 840–845 (2012).
  CAS Google Scholar
• Xiao, C. et al. Defective epithelial barrier function in asthma. J. Allergy Clin. Immunol. 128, 549–556 (2011).
  CAS Google Scholar
• Jacquet, A. Interactions of airway epithelium with protease allergens in the allergic response. Clin. Exp. Allergy 41, 305–311 (2011).
  CAS Google Scholar
• Hackett, T.L. et al. Intrinsic phenotypic differences of asthmatic epithelium and its inflammatory responses to RSV and air pollution. Am. J. Respir. Cell Mol. Biol. 45, 1090–1100 (2011).
  CAS Google Scholar
• Sajjan, U. et al. Rhinovirus disrupts the barrier function of polarized airway epithelial cells. Am. J. Respir. Crit. Care Med. 178, 1271–1281 (2008).
  CAS Google Scholar
• Groschwitz, K.R. & Hogan, S.P. Intestinal barrier function: molecular regulation and disease pathogenesis. J. Allergy Clin. Immunol. 124, 3–20 (2009).
  CAS Google Scholar
• Tieu, D.D. et al. Evidence for diminished levels of epithelial psoriasin and calprotectin in chronic rhinosinusitis. J. Allergy Clin. Immunol. 125, 667–675 (2010).
  CAS Google Scholar
• Hughes, J.L. et al. Reduced structural proteins in the conjunctival epithelium in allergic eye disease. Allergy 61, 1268–1274 (2006).
  CAS Google Scholar
• O'Regan, G.M., Sandilands, A., McLean, W.H. & Irvine, A.D. Filaggrin in atopic dermatitis. J. Allergy Clin. Immunol. 124 (suppl. 2), R2–R6 (2009).
  CAS Google Scholar
• McLean, W.H. The allergy gene: how a mutation in a skin protein revealed a link between eczema and asthma. F1000 Med. Rep. 3, 2 (2011).
  Google Scholar
• Zoltán Veres, T. et al. Spatiotemporal and functional behavior of airway dendritic cells visualized by two-photon microscopy. Am. J. Pathol. 179, 603–609 (2011).
  Google Scholar
• Blank, F. et al. Macrophages and dendritic cells express tight junction proteins and exchange particles in an in vitro model of the human airway wall. Immunobiology 216, 86–95 (2011).
  CAS Google Scholar
• Lambrecht, B.N. & Hammad, H. Biology of lung dendritic cells at the origin of asthma. Immunity 31, 412–424 (2009).
  CAS Google Scholar
• Kassianos, A.J., Jongbloed, S.L., Hart, D.N. & Radford, K.J. Isolation of human blood DC subtypes. Methods Mol. Biol. 595, 45–54 (2010).
  Google Scholar
• Dua, B. et al. Myeloid and plasmacytoid dendritic cells in induced sputum after allergen inhalation in subjects with asthma. J. Allergy Clin. Immunol. 126, 133–139 (2010).
  CAS Google Scholar
• Sha, Q. et al. Activation of airway epithelial cells by Toll-like receptor agonists. Am. J. Respir. Cell Mol. Biol. 31, 358–364 (2004).
  Google Scholar
• Akira, S., Uematsu, S. & Takeuchi, O. Pathogen recognition and innate immunity. Cell 124, 783–801 (2006).
  CAS Google Scholar
• Willart, M.A. & Lambrecht, B.N. The danger within: endogenous danger signals, atopy and asthma. Clin. Exp. Allergy 39, 12–19 (2009).
  CAS Google Scholar
• Lam, D. et al. Airway house dust extract exposures modify allergen-induced airway hypersensitivity responses by TLR4-dependent and independent pathways. J. Immunol. 181, 2925–2932 (2008).
  CAS Google Scholar
• Perros, F., Hoogsteden, H.C., Coyle, A.J., Lambrecht, B.N. & Hammad, H. Blockade of CCR4 in a humanized model of asthma reveals a critical role for DC-derived CCL17 and CCL22 in attracting TH2 cells and inducing airway inflammation. Allergy 64, 995–1002 (2009).
  CAS Google Scholar
• Jackson, D.J. et al. Wheezing rhinovirus illnesses in early life predict asthma development in high-risk children. Am. J. Respir. Crit. Care Med. 178, 667–672 (2008).
  Google Scholar
• Jartti, T. et al. Allergic sensitization is associated with rhinovirus-, but not other virus-, induced wheezing in children. Pediatr. Allergy Immunol. 21, 1008–1014 (2010).
  CAS Google Scholar
• Jackson, D.J. et al. Evidence for a causal relationship between allergic sensitization and rhinovirus wheezing in early life. Am. J. Respir. Crit. Care Med. 185, 281–285 (2012).
  Google Scholar
• Wark, P.A. et al. Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus. J. Exp. Med. 201, 937–947 (2005).
  CAS Google Scholar
• Contoli, M. et al. Role of deficient type III interferon-λ production in asthma exacerbations. Nat. Med. 12, 1023–1026 (2006).
  CAS Google Scholar
• Jartti, T. & Korppi, M. Rhinovirus-induced bronchiolitis and asthma development. Pediatr. Allergy Immunol. 22, 350–355 (2011).
  Google Scholar
• Bosco, A. et al. Decreased activation of inflammatory networks during acute asthma exacerbations is associated with chronic airflow obstruction. Mucosal Immunol. 3, 399–409 (2010).
  CAS Google Scholar
• McWilliam, A.S. et al. Dendritic cells are recruited into the airway epithelium during the inflammatory response to a broad spectrum of stimuli. J. Exp. Med. 184, 2429–2432 (1996).
  CAS Google Scholar
• Uller, L. et al. Double-stranded RNA induces disproportionate expression of thymic stromal lymphopoietin versus interferon-ββ in bronchial epithelial cells from donors with asthma. Thorax 65, 626–632 (2010).
  Google Scholar
• Cakebread, J.A. et al. Exogenous IFN-β has antiviral and anti-inflammatory properties in primary bronchial epithelial cells from asthmatic subjects exposed to rhinovirus. J. Allergy Clin. Immunol. 127, 1148–1154 (2011).
  CAS Google Scholar
• von Mutius, E. & Vercelli, D. Farm living: effects on childhood asthma and allergy. Nat. Rev. Immunol. 10, 861–868 (2010).
  CAS Google Scholar
• Schaub, B. et al. Maternal farm exposure modulates neonatal immune mechanisms through regulatory T cells. J. Allergy Clin. Immunol. 123, 774–782 (2009).
  CAS Google Scholar
• Gern, J.E. Barnyard microbes and childhood asthma. N. Engl. J. Med. 364, 769–770 (2011).
  CAS Google Scholar
• Haahtela, T. Allergy is rare where butterflies flourish in a biodiverse environment. Allergy 64, 1799–1803 (2009).
  CAS Google Scholar
• Rodriguez, B. et al. Germ-free status and altered caecal subdominant microbiota are associated with a high susceptibility to cow's milk allergy in mice. FEMS Microbiol. Ecol. 76, 133–144 (2011).
  CAS Google Scholar
• Hilty, M. et al. Disordered microbial communities in asthmatic airways. PLoS ONE 5, e8578 (2010).
  Google Scholar
• Bisgaard, H. et al. Childhood asthma after bacterial colonization of the airway in neonates. N. Engl. J. Med. 357, 1487–1495 (2007).
  CAS Google Scholar
• Gern, J.E. Barnyard microbes and childhood asthma. N. Engl. J. Med. 364, 769–770 (2011).
  CAS Google Scholar
• Rabinovitch, N. et al. Importance of the personal endotoxin cloud in school-age children with asthma. J. Allergy Clin. Immunol. 116, 1053–1057 (2005).
  CAS Google Scholar
• Platts-Mills, J.A. et al. Airborne endotoxin in homes with domestic animals: implications for cat-specific tolerance. J. Allergy Clin. Immunol. 116, 384–389 (2005).
  CAS Google Scholar
• Shalev, I. et al. Making sense of regulatory T cell suppressive function. Semin. Immunol. 23, 282–292 (2011).
  CAS Google Scholar
• Akdis, C.A. & Akdis, M. Mechanisms of allergen-specific immunotherapy. J. Allergy Clin. Immunol. 127, 18–27 (2011).
  CAS Google Scholar
• Cady, C.T. et al. IgG antibodies produced during subcutaneous allergen immunotherapy mediate inhibition of basophil activation via a mechanism involving both FcγRIIA and FcγRIIB. Immunol. Lett. 130, 57–65 (2010).
  CAS Google Scholar
• Schaub, B. et al. Maternal farm exposure modulates neonatal immune mechanisms through regulatory T cells. J. Allergy Clin. Immunol. 123, 774–782 (2009).
  CAS Google Scholar
• Baru, A.M. et al. Selective depletion of Foxp3+ Treg during sensitization phase aggravates experimental allergic airway inflammation. Eur. J. Immunol. 40, 2259–2266 (2010).
  CAS Google Scholar
• Mold, J.E. et al. Maternal alloantigens promote the development of tolerogenic fetal regulatory T cells in utero. Science 322, 1562–1565 (2008).
  CAS Google Scholar
• Andersson, J. et al. CD4+ FoxP3+ regulatory T cells confer infectious tolerance in a TGF-β–dependent manner. J. Exp. Med. 205, 1975–1981 (2008).
  CAS Google Scholar
• Conrad, M.L. et al. Maternal TLR signaling is required for prenatal asthma protection by the nonpathogenic microbe Acinetobacter lwoffii F78. J. Exp. Med. 206, 2869–2877 (2009).
  CAS Google Scholar
• Brand, S. et al. Epigenetic regulation in murine offspring as a novel mechanism for transmaternal asthma protection induced by microbes. J. Allergy Clin. Immunol. 128, 618–625 (2011).
  CAS Google Scholar
• Rudd, C.E., Taylor, A. & Schneider, H. CD28 and CTLA-4 coreceptor expression and signal transduction. Immunol. Rev. 229, 12–26 (2009).
  CAS Google Scholar
• Kato, A. et al. TLR3- and TH2-cytokine–dependent production of thymic stromal lymphopoietin in human airway epithelial cells. J. Immunol. 179, 1080–1087 (2007).
  CAS Google Scholar
• Liew, F.Y., Pitman, N.I. & McInnes, I.B. Disease-associated functions of IL-33: the new kid in the IL-1 family. Nat. Rev. Immunol. 10, 103–110 (2010).
  CAS Google Scholar
• Wang, Y.H. et al. IL-25 augments type 2 immune responses by enhancing the expansion and functions of TSLP-DC–activated TH2 memory cells. J. Exp. Med. 204, 1837–1847 (2007).
  CAS Google Scholar
• Corrigan, C.J. et al. Allergen-induced expression of IL-25 and IL-25 receptor in atopic asthmatic airways and late-phase cutaneous responses. J. Allergy Clin. Immunol. 128, 116–124 (2011).
  CAS Google Scholar
• Iwakura, Y. et al. Functional specialization of interleukin-17 family members. Immunity 34, 149–162 (2011).
  CAS Google Scholar
• Saenz, S.A. et al. IL25 elicits a multipotent progenitor cell population that promotes TH2 cytokine responses. Nature 464, 1362–1366 (2010).
  CAS Google Scholar
• Neill, D.R. et al. Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity. Nature 464, 1367–1370 (2010).
  CAS Google Scholar
• Barlow, J.L. et al. Innate IL-13–producing nuocytes arise during allergic lung inflammation and contribute to airways hyperreactivity. J. Allergy Clin. Immunol. 129, 191–198 (2012).
  CAS Google Scholar
• Yasuda, K. et al. Contribution of IL-33–activated type II innate lymphoid cells to pulmonary eosinophilia in intestinal nematode-infected mice. Proc. Natl. Acad. Sci. USA 109, 3451–3456 (2012).
  CAS Google Scholar
• Veldhoen, M. et al. Transforming growth factor-β 'reprograms' the differentiation of T helper 2 cells and promotes an interleukin 9–producing subset. Nat. Immunol. 9, 1341–1346 (2008).
  CAS Google Scholar
• Houssiau, F.A. et al. A cascade of cytokines is responsible for IL-9 expression in human T cells. Involvement of IL-2, IL-4, and IL-10. J. Immunol. 154, 2624–2630 (1995).
  CAS Google Scholar
• Goswami, R. et al. STAT6-dependent regulation of TH9 development. J. Immunol. 188, 968–975 (2012).
  CAS Google Scholar
• Faulkner, H., Renauld, J.C., Van Snick, J. & Grencis, R.K. Interleukin-9 enhances resistance to the intestinal nematode Trichuris muris. Infect. Immun. 66, 3832–3840 (1998).
  CAS Google Scholar
• Shimbara, A. et al. IL-9 and its receptor in allergic and nonallergic lung disease: increased expression in asthma. J. Allergy Clin. Immunol. 105, 108–115 (2000).
  CAS Google Scholar
• Erpenbeck, V.J. et al. Segmental allergen challenge in patients with atopic asthma leads to increased IL-9 expression in bronchoalveolar lavage fluid lymphocytes. J. Allergy Clin. Immunol. 111, 1319–1327 (2003).
  CAS Google Scholar
• Bryce, P.J. Revolution 9: the backwards and forwards evidence surrounding interleukin-9. Am. J. Respir. Crit. Care Med. 183, 834–835 (2011).
  Google Scholar
• Steenwinckel, V. et al. IL-13 mediates in vivo IL-9 activities on lung epithelial cells but not on hematopoietic cells. J. Immunol. 178, 3244–3251 (2007).
  CAS Google Scholar
• Kearley, J. et al. IL-9 governs allergen-induced mast cell numbers in the lung and chronic remodeling of the airways. Am. J. Respir. Crit. Care Med. 183, 865–875 (2011).
  CAS Google Scholar
• Parker, J.M. et al. Safety profile and clinical activity of multiple subcutaneous doses of MEDI-528, a humanized anti–interleukin-9 monoclonal antibody, in two randomized phase 2a studies in subjects with asthma. BMC Pulm. Med. 11, 14 (2011).
  CAS Google Scholar
• Harrington, L.E. et al. Interleukin 17–producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat. Immunol. 6, 1123–1132 (2005).
  CAS Google Scholar
• Park, H. et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat. Immunol. 6, 1133–1141 (2005).
  CAS Google Scholar
• Nembrini, C., Marsland, B.J. & Kopf, M. IL-17–producing T cells in lung immunity and inflammation. J. Allergy Clin. Immunol. 123, 986–994 (2009).
  CAS Google Scholar
• Louten, J., Boniface, K. & de Waal Malefyt, R. Development and function of TH17 cells in health and disease. J. Allergy Clin. Immunol. 123, 1004–1011 (2009).
  CAS Google Scholar
• Wilson, R.H. et al. Allergic sensitization through the airway primes TH17-dependent neutrophilia and airway hyperresponsiveness. Am. J. Respir. Crit. Care Med. 180, 720–730 (2009).
  CAS Google Scholar
• Yang, X.O. et al. Regulation of inflammatory responses by IL-17F. J. Exp. Med. 205, 1063–1075 (2008).
  CAS Google Scholar
• Schnyder-Candrian, S. et al. Interleukin-17 is a negative regulator of established allergic asthma. J. Exp. Med. 203, 2715–2725 (2006).
  CAS Google Scholar
• Barlow, J.L. et al. Reciprocal expression of IL-25 and IL-17A is important for allergic airways hyperreactivity. Clin. Exp. Allergy 41, 1447–1455 (2011).
  CAS Google Scholar
• Kudo, M. et al. IL-17A produced by αβ T cells drives airway hyper-responsiveness in mice and enhances mouse and human airway smooth muscle contraction. Nat. Med. 18, 547–554 (2012).
  CAS Google Scholar
• Dunkelberger, J.R. & Song, W.C. Role and mechanism of action of complement in regulating T cell immunity. Mol. Immunol. 47, 2176–2186 (2010).
  CAS Google Scholar
• Humbles, A.A. et al. A role for the C3a anaphylatoxin receptor in the effector phase of asthma. Nature 406, 998–1001 (2000).
  CAS Google Scholar
• Drouin, S.M. et al. Absence of the complement anaphylatoxin C3a receptor suppresses TH2 effector functions in a murine model of pulmonary allergy. J. Immunol. 169, 5926–5933 (2002).
  CAS Google Scholar
• Baelder, R. et al. Pharmacological targeting of anaphylatoxin receptors during the effector phase of allergic asthma suppresses airway hyperresponsiveness and airway inflammation. J. Immunol. 174, 783–789 (2005).
  CAS Google Scholar
• Wills-Karp, M. Complement activation pathways: a bridge between innate and adaptive immune responses in asthma. Proc. Am. Thorac. Soc. 4, 247–251 (2007).
  CAS Google Scholar
• Cosmi, L. et al. Identification of a novel subset of human circulating memory CD4+ T cells that produce both IL-17A and IL-4. J. Allergy Clin. Immunol. 125, 222–230 (2010).
  CAS Google Scholar
• Chakir, J. et al. Airway remodeling-associated mediators in moderate to severe asthma: effect of steroids on TGF-β, IL-11, IL-17, and type I and type III collagen expression. J. Allergy Clin. Immunol. 111, 1293–1298 (2003).
  CAS Google Scholar
• Doe, C. et al. Expression of the T helper 17–associated cytokines IL-17A and IL-17F in asthma and COPD. Chest 138, 1140–1147 (2010).
  CAS Google Scholar
• Chaudhuri, R. et al. Effects of smoking cessation on lung function and airway inflammation in smokers with asthma. Am. J. Respir. Crit. Care Med. 174, 127–133 (2006).
  CAS Google Scholar
• Uddin, M. et al. Enhancement of neutrophil function by the bronchial epithelium stimulated by epidermal growth factor. Eur. Respir. J. 31, 714–724 (2008).
  CAS Google Scholar
• Capone, M. et al. Human invariant V α 24-J α Q TCR supports the development of CD1d-dependent NK1.1+ and NK1.1− T cells in transgenic mice. J. Immunol. 170, 2390–2398 (2003).
  CAS Google Scholar
• Brennan, P.J. et al. Invariant natural killer T cells recognize lipid self antigen induced by microbial danger signals. Nat. Immunol. 12, 1202–1211 (2011).
  CAS Google Scholar
• Meyer, E.H. et al. Glycolipid activation of invariant T cell receptor+ NK T cells is sufficient to induce airway hyperreactivity independent of conventional CD4+ T cells. Proc. Natl. Acad. Sci. USA 103, 2782–2787 (2006).
  CAS Google Scholar
• Akbari, O. et al. CD4+ invariant T-cell-receptor+ natural killer T cells in bronchial asthma. N. Engl. J. Med. 354, 1117–1129 (2006).
  CAS Google Scholar
• Vijayanand, P. et al. Invariant natural killer T cells in asthma and chronic obstructive pulmonary disease. N. Engl. J. Med. 356, 1410–1422 (2007).
  CAS Google Scholar
• Wingender, G. et al. Invariant NKT cells are required for airway inflammation induced by environmental antigens. J. Exp. Med. 208, 1151–1162 (2011).
  CAS Google Scholar
• Altin, J., Shen, C. & Liston, A. Understanding the genetic regulation of IgE production. Blood Rev. 24, 163–169 (2010).
  CAS Google Scholar
• Xiong, H. et al. Sequential class switching is required for the generation of high affinity IgE antibodies. J. Exp. Med. 209, 353–364 (2012).
  CAS Google Scholar
• Acharya, M. et al. CD23/FcɛRII: molecular multi-tasking. Clin. Exp. Immunol. 162, 12–23 (2010).
  CAS Google Scholar
• Ying, S. et al. Local expression of epsilon germline gene transcripts and RNA for the ɛ heavy chain of IgE in the bronchial mucosa in atopic and nonatopic asthma. J. Allergy Clin. Immunol. 107, 686–692 (2001).
  CAS Google Scholar
• Barnes, P.J. Intrinsic asthma: not so different from allergic asthma but driven by superantigens? Clin. Exp. Allergy 39, 1145–1151 (2009).
  CAS Google Scholar
• Bel, E. & ten Brinke, A. A rational approach to the management of severe refractory asthma. Treat. Respir. Med. 4, 365–379 (2005).
  Google Scholar
• Kon, O.M. et al. Randomised, dose-ranging, placebo-controlled study of chimeric antibody to CD4 (keliximab) in chronic severe asthma. Lancet 352, 1109–1113 (1998).
  CAS Google Scholar
• Kon, O.M. et al. The effects of an anti-CD4 monoclonal antibody, keliximab, on peripheral blood CD4+ T cells in asthma. Eur. Respir. J. 18, 45–52 (2001).
  CAS Google Scholar
• Wang, X.F. et al. Interleukin-2 receptor antagonists in liver transplantation: a meta-analysis of randomized trials. Transplant. Proc. 42, 4567–4572 (2010).
  CAS Google Scholar
• Busse, W.W. et al. Daclizumab improves asthma control in patients with moderate to severe persistent asthma: a randomized, controlled trial. Am. J. Respir. Crit. Care Med. 178, 1002–1008 (2008).
  CAS Google Scholar
• Panina-Bordignon, P. et al. The C–C chemokine receptors CCR4 and CCR8 identify airway T cells of allergen-challenged atopic asthmatics. J. Clin. Invest. 107, 1357–1364 (2001).
  CAS Google Scholar
• Vijayanand, P. et al. Chemokine receptor 4 plays a key role in T cell recruitment into the airways of asthmatic patients. J. Immunol. 184, 4568–4574 (2010).
  CAS Google Scholar
• Reyes, C.L. Americas Antibody Congress 2009. 21–23 September 2009, Washington DC, USA. IDrugs 12, 692–694 (2009).
  Google Scholar
• Yano, H. et al. Defucosylated anti CC chemokine receptor 4 monoclonal antibody combined with immunomodulatory cytokines: a novel immunotherapy for aggressive/refractory Mycosis fungoides and Sezary syndrome. Clin. Cancer Res. 13, 6494–6500 (2007).
  CAS Google Scholar
• Matsuoka, T. et al. Prostaglandin D2 as a mediator of allergic asthma. Science 287, 2013–2017 (2000).
  CAS Google Scholar
• Arima, M. & Fukuda, T. Prostaglandin D2 receptors DP and CRTH2 in the pathogenesis of asthma. Curr. Mol. Med. 8, 365–375 (2008).
  CAS Google Scholar
• Gervais, F.G. et al. Pharmacological characterization of MK-7246, a potent and selective CRTH2 (chemoattractant receptor-homologous molecule expressed on T-helper type 2 cells) antagonist. Mol. Pharmacol. 79, 69–76 (2011).
  CAS Google Scholar
• Barnes, N. et al. A randomized, double-blind, placebo-controlled study of the CRTH2 antagonist OC000459 in moderate persistent asthma. Clin. Exp. Allergy 42, 38–48 (2012).
  CAS Google Scholar
• Karman, J. et al. Ligation of cytotoxic T lymphocyte antigen-4 to the TCR inhibits T cell activation and directs differentiation into FOXP3+ regulatory T cells. J. Biol. Chem. published online (15 February 2012), doi:10.1074/jbc.M111.283705.
  CAS Google Scholar
• Álvarez-Quiroga, C. et al. CTLA-4-Ig therapy diminishes the frequency but enhances the function of Treg cells in patients with rheumatoid arthritis. J. Clin. Immunol. 31, 588–595 (2011).
  Google Scholar
• Bour-Jordan, H. et al. Costimulation controls diabetes by altering the balance of pathogenic and regulatory T cells. J. Clin. Invest. 114, 979–987 (2004).
  CAS Google Scholar
• Jaffar, Z.H. et al. Essential role for both CD80 and CD86 costimulation, but not CD40 interactions, in allergen-induced TH2 cytokine production from asthmatic bronchial tissue: role for αβ, but not γδ, T cells. J. Immunol. 163, 6283–6291 (1999).
  CAS Google Scholar
• Hidi, R. et al. Role of B7–CD28/CTLA-4 costimulation and NF-κB in allergen-induced T cell chemotaxis by IL-16 and RANTES. J. Immunol. 164, 412–418 (2000).
  CAS Google Scholar
• Lordan, J.L. et al. The role of CD28–B7 costimulation in allergen-induced cytokine release by bronchial mucosa from patients with moderately severe asthma. J. Allergy Clin. Immunol. 108, 976–981 (2001).
  CAS Google Scholar
• Holgate, S.T. Pathophysiology of asthma: what has our current understanding taught us about new therapeutic approaches? J. Allergy Clin. Immunol. 128, 495–505 (2011).
  CAS Google Scholar
• Hansbro, P.M., Kaiko, G.E. & Foster, P.S. Cytokine/anti-cytokine therapy—novel treatments for asthma? Br. J. Pharmacol. 163, 81–95 (2011).
  CAS Google Scholar
• Berry, M.A. et al. Sputum and bronchial submucosal IL-13 expression in asthma and eosinophilic bronchitis. J. Allergy Clin. Immunol. 114, 1106–1109 (2004).
  CAS Google Scholar
• Woodruff, P.G. et al. T-helper type 2–driven inflammation defines major subphenotypes of asthma. Am. J. Respir. Crit. Care Med. 180, 388–395 (2009).
  CAS Google Scholar
• Corren, J. et al. Lebrikizumab treatment in adults with asthma. N. Engl. J. Med. 365, 1088–1098 (2011).
  CAS Google Scholar
• Nair, P. et al. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N. Engl. J. Med. 360, 985–993 (2009).
  CAS Google Scholar
• Haldar, P. et al. Mepolizumab and exacerbations of refractory eosinophilic asthma. N. Engl. J. Med. 360, 973–984 (2009).
  CAS Google Scholar
• Abonia, J.P. & Putnam, P.E. Mepolizumab in eosinophilic disorders. Expert Rev. Clin. Immunol. 7, 411–417 (2011).
  CAS Google Scholar
• Castro, M. et al. Reslizumab for poorly controlled, eosinophilic asthma: a randomized, placebo-controlled study. Am. J. Respir. Crit. Care Med. 184, 1125–1132 (2011).
  CAS Google Scholar
• Spergel, J.M. et al. Reslizumab in children and adolescents with eosinophilic esophagitis: Results of a double-blind, randomized, placebo-controlled trial. J. Allergy Clin. Immunol. 129, 456–463 (2012).
  CAS Google Scholar
• Gevaert, P. et al. Nasal IL-5 levels determine the response to anti–IL-5 treatment in patients with nasal polyps. J. Allergy Clin. Immunol. 118, 1133–1141 (2006).
  CAS Google Scholar
• Kolbeck, R. et al. MEDI-563, a humanized anti–IL-5 receptor α mAb with enhanced antibody-dependent cell-mediated cytotoxicity function. J. Allergy Clin. Immunol. 125, 1344–1353 (2010).
  CAS Google Scholar
• Busse, W.W. et al. Safety profile, pharmacokinetics, and biologic activity of MEDI-563, an anti–IL-5 receptor α antibody, in a phase I study of subjects with mild asthma. J. Allergy Clin. Immunol. 125, 1237–1244 (2010).
  CAS Google Scholar
• Wenzel, S.E. et al. A randomized, double-blind, placebo-controlled study of tumor necrosis factor-α blockade in severe persistent asthma. Am. J. Respir. Crit. Care Med. 179, 549–558 (2009).
  CAS Google Scholar
• Silvestri, M. et al. High serum levels of tumour necrosis factor-α and interleukin-8 in severe asthma: markers of systemic inflammation? Clin. Exp. Allergy 36, 1373–1381 (2006).
  CAS Google Scholar
• Baines, K.J. et al. Differential gene expression and cytokine production from neutrophils in asthma phenotypes. Eur. Respir. J. 35, 522–531 (2010).
  CAS Google Scholar
• Holmes, A.M., Solari, R. & Holgate, S.T. Animal models of asthma: value, limitations and opportunities for alternative approaches. Drug Discov. Today 16, 659–670 (2011).
  Google Scholar