Beruflich Dokumente
Kultur Dokumente
IMMUNOLOGY IN JAPAN
REVIEW
3
Toyama Prefectural Institute of Pharmaceutical Research, 17-1 Naka-Taikoyama, Imizu-shi, Toyama 939-0363, Japan
Introduction
IL-5 was originally found as T-cell replacing factor that is ces signals for multiple functions (6, 811). The IL-5Ra
secreted from T cells to stimulate antibody production from specifically binds to IL-5 and the bc is a molecule shared
activated B cells (1). IL-5 is produced by Th2 cells after with other cytokine receptors, including IL-3R and granulo-
stimulation with Mycobacterium tuberculosis, Toxocara canis cyte/macrophage colony-stimulating factor (GM-CSF) recep-
or with allergens and by mast cells upon stimulation with tor. The bc alone does not bind any cytokines, has relatively
allergenIgE complex (2). As an active form, IL-5 makes long cytoplasmic portion and several functional domains
homodimer in that two molecules are coupled in interdigi- (11, 12) and is deeply involved in the signal transduction
tated fashion. IL-5 messenger RNA (mRNA) is also (Fig. 1). Intriguingly, the cytoplasmic region of IL-5Ra, partic-
expressed in eosinophils, cdT cells, NK and NKT cells and ularly the membrane-proximal proline-rich sequences, is
non-hematopoietic cells (36). CD4 c-kit CD3e IL-2Ra+ required for IL-5-induced cellular proliferation and signal
cells in the Peyers patch produce high levels of IL-5 when transduction (1316).
stimulated with IL-2 (7). IL-5 induces terminal differentiation of activated B cells
IL-5 acts on target cells by binding to its specific receptor into antibody-forming cells in mice and enhances prolifera-
(IL-5R). The IL-5R consists of a unique a chain (IL-5Ra/ tion and differentiation of eosinophil precursors into mature
CD125) and the common cytokine b-chain (bc/CD131) and eosinophils in mice and humans. B-1 cells, which are distin-
is expressed on cells in various lineages, where it transdu- guishable from B-2 cells by their cell surface markers,
Correspondence to: K. Takatsu; E-mail: takatsuk@med.u-toyama.ac.jp Received 7 August 2009, accepted 18 September 2009
Advance Access publication 9 October 2009
1304 IL-5 in allergic inflammation
anatomical location and self-replenishing activity, constitu- in the airways of asthmatics by targeting IL-5 have only had
tively express IL-5Ra and respond to IL-5 for survival, prolif- limited success (34).
eration and differentiation to antibody-secreting plasma cells In this review, we will describe recent progress in several
(17, 18). IL-5Ra / and IL-5 / mice show a decrease in B- aspects of eosinophil function in allergic inflammation in
1 cells in peritoneal washouts and in B-1-cell-derived sIgA+ conjunction with the function of IL-5. We will also discuss
cells in lamina propria (1921). B-2 cells activated by anti- the role of IL-5 in allergic inflammation as a novel molecular
gen or mitogens in the presence of Th cells express IL-5Ra target for therapy of allergic inflammation with particular em-
and become responsive to IL-5 for maturation (22, 23). It still phasis on anti-IL-5 therapy.
remains elusive whether human activated B cells express IL-
5Ra and respond to IL-5 for maturation. In both mice and IL-5 in eosinophil differentiation and survival
humans, IL-5Ra is expressed on mature eosinophils and
basophils. Eosinophils diverge from hematopoietic stem cells (HSCs).
Allergic diseases, including asthma, are characterized by The effects of IL-5 on eosinophils largely fall into four cate-
inflammation with pronounced infiltration of eosinophils and gories, namely differentiation, migration, activation and
CD4+ T cells (24, 25). Regarding the inflammatory cells survival. As for differentiation, IL-5 is not an inducer of eosin-
implicated in asthma, recruitment of CD4+ Th2 cells and ophil lineage commitment but rather an enhancing factor for
eosinophils is a central feature of the late-phase allergic differentiation and proliferation of eosinophil progenitors
response (LAR) (24, 26). Accumulating evidence indicates (EoPs) (32, 3537). Although helminth infection-induced eo-
that classical Th2-cell-derived cytokines (e.g. IL-3, IL-4, IL-5, sinophil production was impaired, IL-5-deficient or IL-5R-