Antichemokine immunotherapy for allergic diseases : Current Opinion in Allergy and Clinical Immunology (original) (raw)

Review Article

Correspondence to Andrew D. Luster, Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA e-mail: [email protected]

Abbreviations

BLC: B lymphocyte chemoattractant

CCR: CC chemokine receptor

CLA: cutaneous lymphocyte antigen

CXCR: CXC chemokine receptor

DC-CK1: dendritic cell-derived CC chemokine 1

ELC: Epstein-Barr virus induced gene ligand 1 chemokine

MCP: monocyte chemoattractant protein

MDC: macrophage-derived chemokine

MIP: macrophage inflammatory protein

RANTES: regulated upon activation in normal T cells expressed and secreted

SLC: secondary lymphoid chemokine

STAT6: signal transducer and activator of transcription factor 6

TARC: thymus- and activation-regulated chemokine

Th2: T helper type 2

Abstract

Chemokines have emerged as critical regulators of leukocyte function and as such represent attractive new targets for the therapy of allergic diseases. Recent studies have revealed important roles for the chemokine family in both the afferent and efferent limbs of the immune system, orchestrating and integrating innate and acquired immune responses. A subset of chemokines including eotaxin-1 (also called CCL11), eotaxin-2 (CCL24), eotaxin-3 (CCL26), MCP (monocyte chemoattractant protein)-3 (CCL7), MCP (monocyte chemoattractant protein)-4 (CCL13), TARC (thymus- and activation-regulated chemokine) (CCL17), and MDC (macrophage-derived chemokine) (CCL22) are highly expressed in allergic inflammation and are regulated by T helper type 2 cytokines. Receptors for these chemokines, including CCR3 (CC chemokine receptor 3), CCR4 (CC chemokine receptor 4) and CCR8 (CC chemokine receptor 8) are expressed on key leukocytes associated with allergic inflammation, such as T helper type 2 cells, eosinophils, mast cells and basophils, establishing a subset of chemokine/chemokine receptors potentially important in allergic inflammation. Recent data using inhibitory antibodies and chemokine antagonists support the concept that interfering with this subset of chemokines and their receptors represents a new approach to allergy immunotherapy.