Elsevier

Current Opinion in Immunology

Volume 11, Issue 6, 1 December 1999, Pages 626-634
Current Opinion in Immunology

Review
Chemokines in allergy

https://doi.org/10.1016/S0952-7915(99)00028-XGet rights and content

Abstract

Knowledge of the chemokine superfamily has undergone a dramatic expansion during the past decade. Currently, we are witnessing a transition from a phase of molecular discovery to a phase of disease associations and the establishment of functional (clinical) relevance. Recent data regarding the expression of chemokines and their receptors in pathologically relevant cells as well as observations using gene-targeting approaches have given us a better understanding of the complex mechanisms involved in leukocyte recruitment and inflammation as well as their potential role in the immunopathogenesis of human diseases.

Introduction

During recent years the prevalence of atopic and allergic diseases has increased rapidly in developed countries. These diseases represent complex and chronic inflammatory disorders that involve the recruitment and activation of many inflammatory and structural cells, all of which release inflammatory mediators that result in the typical pathophysiological changes observed in the airways or skin. Along with adhesion molecules, chemokines and their receptors are believed to be essential for leukocyte trafficking from the circulation into inflammatory tissues. This report represents a brief summary of the association of chemokines and their receptors with atopic diseases such as asthma and atopic dermatitis. Based on these data, we propose two models for the potential roles of chemokines and their receptors in these diseases (depicted in Figure 1, Figure 2).

Section snippets

The chemokine and chemokine receptor superfamily: current status

Chemokines are small, secreted proteins that regulate leukocyte trafficking. Recently, knowledge of this superfamily has grown significantly due to the availability of large databases of expressed sequence tags (ESTs) and bioinformatics [1••]. In fact the chemokines are probably the best example of the impact of these new gene-discovery methods, since their structural features make it easy to recognize new members in EST databases. These chemoattractants share structural similarities, including

Chemokine receptors and Th1 and Th2 cells

Th2 cells have been shown to play an important role in atopy and allergic diseases. In contrast, delayed-type hypersensitivity reactions — such as contact allergic responses — are believed to be mediated by Th1 cells.

Recently, several groups investigated the chemokine receptors expressed by Th1 cells compared with Th2 cells. Sallusto et al. [2] showed that human IL-4-producing cells express CCR3, suggesting that Th2 cells express this marker. Using northern blot analysis, Bonecchi et al. [3]

Chemokines and their receptors in the pathogenesis of atopic asthma

Asthma represents a chronic inflammatory lung disease with T-cell-mediated inflammation of the bronchial mucosa characterized by an influx of eosinophils [9]. Eosinophils are thought to be the primary cells responsible for the induction of bronchial mucosal injury and are associated with bronchial obstruction during asthmatic responses 10, 11. In atopic (‘allergic’) asthma, production of Th2 cytokines — such as IL-4 and IL-5 — correlates with disease severity and eosinophil infiltration 9, 12,

Chemokines and their receptors in the pathogenesis of atopic dermatitis

Atopic dermatitis represents one of the most common skin diseases, with a lifetime prevalence of up to 20% 44, 45 and an increasing number of cases 46, 47, 48. Clinically this chronic or chronically relapsing inflammatory skin disease is characterized by eczematous lesions with typical morphology and distribution, severe pruritus, elevated serum IgE, the presence of allergen-specific IgE and peripheral blood eosinophilia [49]. Histopathologically, the lesional skin of atopic dermatitis patients

Conclusions

What we can learn from studying chemokines and chemokine receptors in the complex immunopathogenesis of atopic diseases is that these mediators most probably work in an interdependent fashion and their sequential (orchestrated) production will contribute to inflammatory processes that develop into the disease phenotype. Future studies will address questions about the chemokine receptors responsible for Th2 cell recruitment in vivo, whether viral chemokines contribute to disease

Acknowledgements

DNAX Research Institute is supported by the Schering-Plough Corporation (Madison, New Jersey). We thank Edith Hessel and Luis Teran for comments and Maribel Andonian for her help with the illustrations. We thank O Yoshie for proposing the new chemokine nomenclature.

References and recommended reading

Papers of particular interest, published within the annual period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

References (67)

  • F.L. van der Heijden et al.

    High frequency of IL-4-producing CD4+ allergen-specific T lymphocytes in atopic dermatitis lesional skin

    J Invest Dermatol

    (1991)
  • F.C. van Reijsen et al.

    Skin-derived aeroallergen-specific T-cell clones of Th2 phenotype in patients with atopic dermatitis

    J Allergy Clin Immunol

    (1992)
  • M. Grewe et al.

    Lesional expression of interferon-gamma in atopic eczema

    Lancet

    (1994)
  • N. Yawalkar et al.

    Enhanced expression of eotaxin and CCR3 in atopic dermatitis

    J Invest Dermatol

    (1999)
  • A. Zlotnik et al.

    Recent advances in chemokines and chemokine receptors

    Crit Rev Immunol

    (1999)
  • F. Sallusto et al.

    Selective expression of the eotaxin receptor CCR3 by human T helper 2 cells

    Science

    (1997)
  • R. Bonecchi et al.

    Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s

    J Exp Med

    (1998)
  • J.T. Siveke et al.

    T helper 1 and T helper 2 cells respond differentially to chemokines

    J Immunol

    (1998)
  • A. Zingoni et al.

    The chemokine receptor CCR8 is preferentially expressed in Th2 but not Th1 cells

    J Immunol

    (1998)
  • W.J. Karpus et al.

    Monocyte chemotactic protein 1 regulates oral tolerance induction by inhibition of T helper cell 1-related cytokines

    J Exp Med

    (1998)
  • W.J. Karpus et al.

    Differential CC chemokine-induced enhancement of T helper cell cytokine production

    J Immunol

    (1997)
  • B. Lu et al.

    Abnormalities in monocyte recruitment and cytokine expression in monocyte chemoattractant protein 1- deficient mice

    J Exp Med

    (1998)
  • G.J. Gleich et al.

    The biology of the eosinophilic leukocyte

    Annu Rev Med

    (1993)
  • A.B. Kay et al.

    Asthma. Eosinophils and neutrophils

    Br Med Bull

    (1992)
  • C.J. Corrigan et al.

    Asthma. Role of T-lymphocytes and lymphokines

    Br Med Bull

    (1992)
  • G. Del Prete

    Human Th1 and Th2 lymphocytes: their role in the pathophysiology of atopy

    Allergy

    (1992)
  • C. Gratziou et al.

    Inflammatory T cell profile of asthmatic airways 6 hours after local allergen provocation

    Am J Respir Crit Care Med

    (1996)
  • D.S. Robinson et al.

    Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma

    N Engl J Med

    (1992)
  • S. Romagnani et al.

    Increased numbers of Th2-like CD4+ T cells in target organs and in the allergen-specific repertoire of allergic patients. Possible role of IL-4 produced by non-T cells

    Int Arch Allergy Appl Immunol

    (1991)
  • C. Walker et al.

    T cells and asthma. II. Regulation of the eosinophilia of asthma by T cell cytokines

    Int Arch Allergy Appl Immunol

    (1991)
  • X. Zhang et al.

    T cells from atopic individuals produce IgE-inducing activity incompletely blocked by anti-interleukin-4 antibody

    Eur J Immunol

    (1992)
  • S.H. Gavett et al.

    Depletion of murine CD4+ T lymphocytes prevents antigen-induced airway hyperreactivity and pulmonary eosinophilia

    Am J Respir Cell Mol Biol

    (1994)
  • I. Iwamoto et al.

    Role of CD4+ T lymphocytes and interleukin-5 in antigen-induced eosinophil recruitment into the site of cutaneous late-phase reaction in mice

    J Leukoc Biol

    (1992)
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