International Immunology, Vol. 21, No. 12, pp. 1303–1309
ª The Japanese Society for Immunology. 2009. All rights reserved.
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IMMUNOLOGY IN JAPAN
IL-5- and eosinophil-mediated inflammation: from
discovery to therapy
Taku Kouro1and Kiyoshi Takatsu2,3
1Laboratory of Immune Modulation, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085,
2Department of Immunobiology and Pharmacological Genetics, Graduate School of Medicine and Pharmaceutical Science,
University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan
3Toyama Prefectural Institute of Pharmaceutical Research, 17-1 Naka-Taikoyama, Imizu-shi, Toyama 939-0363, Japan
Keywords: airway, B cell, cytokine, eosinophil, Th1/Th2
IL-5 was originally defined as a T-cell-derived cytokine that triggers activated B cells for terminal
differentiation into antibody-secreting plasma cells, at least in mice. Concurrently, IL-5 was
recognized as the major maturation and differentiation factor for eosinophils in mice and humans.
Over-expression of IL-5 significantly increases eosinophil numbers and antibody levels in vivo.
Conversely, mice lacking a functional gene for IL-5 or the IL-5 receptor alpha chain (IL-5Ra) display
a number of developmental and functional impairments in B-cell and eosinophil lineages. In addition
to the Janus kinase–signal transducer and activator of transcription pathway, the tyrosine kinases
Lyn and Btk (Bruton agammaglobulinemia tyrosine kinase) are involved, and Ras GTPase–
extracellular signal-regulated kinase (Ras–ERK) signals are important for IL-5-dependent cell
proliferation and survival. IL-5 critically regulates expression of genes involved in proliferation, cell
survival and maturation and effector functions of B cells and eosinophils. Thus, IL-5 plays a pivotal
role in innate and acquired immune responses and eosinophilia. In humans, the biologic effects of
IL-5 are best characterized for eosinophils. The recent expansion in our understanding of the
mechanisms of eosinophil development and activation in the context of IL-5 has led to advances in
therapeutic options. A new therapy currently in clinical trials uses humanized mAbs against IL-5 or
IL-5 was originally found as ‘T-cell replacing factor’ that is
secreted from T cells to stimulate antibody production from
activated B cells (1). IL-5 is produced by Th2 cells after
stimulation with Mycobacterium tuberculosis, Toxocara canis
or with allergens and by mast cells upon stimulation with
allergen–IgE complex (2). As an active form, IL-5 makes
homodimer in that two molecules are coupled in ‘interdigi-
expressed in eosinophils, cdT cells, NK and NKT cells and
non-hematopoietic cells (3–6). CD4?c-kit?CD3e?IL-2Ra+
cells in the Peyer’s patch produce high levels of IL-5 when
stimulated with IL-2 (7).
IL-5 acts on target cells by binding to its specific receptor
(IL-5R). The IL-5R consists of a unique a chain (IL-5Ra/
CD125) and the common cytokine b-chain (bc/CD131) and
is expressed on cells in various lineages, where it transdu-
ces signals for multiple functions (6, 8–11). The IL-5Ra
specifically binds to IL-5 and the bc is a molecule shared
with other cytokine receptors, including IL-3R and granulo-
cyte/macrophage colony-stimulating factor (GM-CSF) recep-
tor. The bc alone does not bind any cytokines, has relatively
long cytoplasmic portion and several functional domains
(11, 12) and is deeply involved in the signal transduction
(Fig. 1). Intriguingly, the cytoplasmic region of IL-5Ra, partic-
ularly the membrane-proximal proline-rich sequences, is
required for IL-5-induced cellular proliferation and signal
IL-5 induces terminal differentiation of activated B cells
into antibody-forming cells in mice and enhances prolifera-
tion and differentiation of eosinophil precursors into mature
eosinophils in mice and humans. B-1 cells, which are distin-
guishable from B-2 cells by their cell surface markers,
Correspondence to: K. Takatsu; E-mail: firstname.lastname@example.orgReceived 7 August 2009, accepted 18 September 2009
Advance Access publication 9 October 2009
by guest on June 8, 2013
anatomical location and self-replenishing activity, constitu-
tively express IL-5Ra and respond to IL-5 for survival, prolif-
eration and differentiation to antibody-secreting plasma cells
(17, 18). IL-5Ra?/?and IL-5?/?mice show a decrease in B-
1 cells in peritoneal washouts and in B-1-cell-derived sIgA+
cells in lamina propria (19–21). B-2 cells activated by anti-
gen or mitogens in the presence of Th cells express IL-5Ra
and become responsive to IL-5 for maturation (22, 23). It still
remains elusive whether human activated B cells express IL-
5Ra and respond to IL-5 for maturation. In both mice and
humans, IL-5Ra is expressed on mature eosinophils and
Allergic diseases, including asthma, are characterized by
inflammation with pronounced infiltration of eosinophils and
CD4+T cells (24, 25). Regarding the inflammatory cells
implicated in asthma, recruitment of CD4+Th2 cells and
eosinophils is a central feature of the late-phase allergic
response (LAR) (24, 26). Accumulating evidence indicates
that classical Th2-cell-derived cytokines (e.g. IL-3, IL-4, IL-5,
IL-9, IL-13 and GM-CSF) together with eotaxin play critical
roles in the induction of airway hyper-reactivity and the
development of chronic airway wall remodeling (27–29). In
addition, newly identified cytokines, including thymic stromal
lymphopoietin, IL-25 and IL-33, are involved in the induction
of allergic inflammation in asthma (30–32).
Eosinophils possess distinctive granule proteins, including
major basic protein, eosinophil peroxidase and eosinophil-
derived neurotoxin. In both mice and humans, IL-5 induces
terminal maturation of eosinophils, prolongs eosinophil
survival by delaying apoptotic death, possesses eosinophil
chemotactic activity, increases eosinophil adhesion to endo-
thelial cells and enhances eosinophil effector functions (28,
33). However, attempts to inhibit accumulation of eosinophils
in the airways of asthmatics by targeting IL-5 have only had
limited success (34).
In this review, we will describe recent progress in several
aspects of eosinophil function in allergic inflammation in
conjunction with the function of IL-5. We will also discuss
the role of IL-5 in allergic inflammation as a novel molecular
target for therapy of allergic inflammation with particular em-
phasis on anti-IL-5 therapy.
IL-5 in eosinophil differentiation and survival
Eosinophils diverge from hematopoietic stem cells (HSCs).
The effects of IL-5 on eosinophils largely fall into four cate-
gories, namely differentiation, migration, activation and
survival. As for differentiation, IL-5 is not an inducer of eosin-
ophil lineage commitment but rather an enhancing factor for
differentiation and proliferation of eosinophil progenitors
(EoPs) (32, 35–37). Although helminth infection-induced eo-
sinophil production was impaired, IL-5-deficient or IL-5R-
deficient mice showed a steady state of eosinophilopoiesis,
suggesting that factors or cytokines other than IL-5 may be
involved in, or compensate for, the constitutive generation of
eosinophils at basal levels (19, 20).
IL-5-mediated signal transduction
It is well accepted that IL-5Ra expression in the bone mar-
row cells is one of most critical issues in eosinophil lineage
commitment (Fig. 2). The regulatory factor X (RFX) family
DNA-binding proteins were shown to bind to cis element of
IL-5Ra promoter (38). Although expression of RFX proteins
Fig. 1. Signal transduction pathways of IL-5 in the eosinophils. IL-5
and its two receptor chains (IL-5Ra and bc) are shown in the cell
membrane, and signals in the cytoplasm and nucleus are indicated.
Red ovals represent signaling molecules and purple rectangles show
the effect of each signal. STAT* indicates STAT1, STAT3 or STAT5.
Molecules specific to IL-5 signaling in B cells or reported only in
B cells, such as Btk and Vav, are omitted.
Fig. 2. Differentiation of eosinophils in fetal and adult hematopoiesis.
EoPs are GMPs that express IL-5Ra. Note that sub-population of ProB
cells also express IL-5Ra and differentiate to B-1 cells. Since lineage
commitment is not final and can be reversed in certain environment
even at CLP stage, reversibility of progenitors is shown by background
green structure. CMP, common myeloid progenitor; Eo, eosinophil;
Neu, neutrophil; Baso, basophil; Mono, monocyte; MEP, megakaryo-
cyte/erythroid progenitor; MK, megakaryocyte; Ery, erythrocyte; ELP,
early lymphoid progenitor; ETP, early T-cell progenitor; ProT, progenitor
T cell; T, T lymphocyte; CLP, common lymphoid progenitor; ProB,
progenitor B cell; B, B lymphocyte.
1304IL-5 in allergic inflammation
by guest on June 8, 2013
is ubiquitous, they are suggested to act as lineage-specific
activators in cooperation with other factors. Although Oct2
was found to be indispensable for expression of IL-5Ra in B
cells (39), a lineage-specific activator of IL-5Ra transcription
in eosinophils so far remains obscure. As for down-regulation
of IL-5Ra, all-trans retinoic acid is reported to suppress eosi-
nophilopoiesis by down-regulating membrane-bound IL-5Ra
and up-regulating the soluble form of IL-5Ra (40).
IL-5 stimulation induces rapid tyrosine phosphorylation of
(Fig. 1): bc; Src-homology 2 (SH2)/SH3-containing proteins
such as Vav guanine nucleotide exchange factor, HS1
(hematopoietic lineage cell-specific protein 1) and Shc (Src-
(Bruton agammaglobulinemia tyrosine kinase) and Btk-
associated molecules; JAK1 (Janus kinase 1), JAK2, STAT1
(signal transducer and activator of transcription 1) STAT3
and STAT5; phosphoinositide 3-kinase (PI3K); Lyn tyrosine
kinase and mitogen-activated protein kinases (MAPKs).
Phosphorylation of these molecules results in activation of
downstream signaling molecules (12–15, 41, 42). In addition,
IL-5 activates Raf-1 (v-raf-1 murine leukemia viral oncogene
homolog 1) and the phosphatase SHP2 (Src-homology-2-
domain-containing protein tyrosine phosphatase) (43).
The activation of JAK2 and STAT5 is essential for IL-5-
dependent signal transduction both in B cells and in
eosinophils (44, 45). IL-5 also induces the expression of
CIS (cytokine-inducible SH2 protein) and JAB (JAK-
binding protein) in eosinophils; this is one of the feedback
loops of negative regulation of IL-5 signaling (46). In addi-
tion to the JAK2–STAT5 pathway, the Ras GTPase–
extracellular signal-regulated kinase (Ras–ERK) pathway
has also been implicated in signaling of IL-5 (47) and is
important for IL-5-dependent cell survival, proliferation
and differentiation of eosinophils. JAK2 and Lyn appear to
be important for cell proliferation and survival, whereas
Raf-1 seems to play a central role in regulating cell func-
tion, such as degranulation.
Our analyses of functional cytoplasmic domains of human
(hIL-5Ra) that regulate
revealed that JAK2 is constitutively associated with hIL-5Ra
regardless of IL-5 stimulation. In contrast, JAK1 is constitu-
tively associated with bc regardless of IL-5 stimulation and
is associated with hIL-5Ra only when cells are stimulated
with IL-5 (15). Both JAK1 and JAK2 are activated upon stim-
ulation with IL-5. These results clearly indicate that JAK2 and
JAK1 are constitutively associated with hIL-5Ra and bc,
respectively, and that they construct a functional hIL-5Ra–bc
complex in the presence IL-5. The region of hIL-5Ra neces-
sary for JAK2 binding is located in amino acid residues
346–387, which include proline-rich sequences, of the
cytoplasmic domain (Fig. 1).
Signaling by bc is terminated partially by ubiquitination
and proteasome degradation of its cytoplasmic domain,
resulting in the generation of truncated bc products, termed
bc intra-cytoplasmic proteolysis (bIP) (48). Moreover, inhibi-
tion of bc proteasome degradation resulted in prolonged
activation of bc, JAK2, STAT5 and SHP2. JAK kinase activity
is required for the direct ubiquitination of the bc cytoplasmic
region and proteasome degradation.
JAK kinase activation
Spred-1 (sprouty-related enabled/vasodilator-stimulated phos-
phoprotein homology 1 domain-containing 1) is a negative regu-
lator of growth-factor-mediated, Ras-dependent ERK activation.
Spred-1-deficient mice show enhanced allergen-induced air-
way eosinophilia and hyper-responsiveness without affecting
helper T-cell differentiation. Biochemical analysis revealed that
Spred-1 suppresses IL-5-dependent cell proliferation and ERK
activation (49), indicating that Spred-1 is a negative regulator
of IL-5-induced eosinophil activation.
Activation of IL-5R upon IL-5 stimulation triggers tyrosine
phosphorylation of signaling molecules in several pathways
that differ between B cells and eosinophils. Btk activation is
indispensable for IL-5-induced proliferation and differentia-
tion in mouse B cells. The B cells in X-linked immunodefi-
ciency (XID) mice, in which Btk contains a single amino
acid mutation in the pleckstrin-homology domain, show im-
paired signal transduction through the B cell receptor and
IL-5R (42, 50). Interestingly, EoPs in the bone marrow of XID
mice and their mature eosinophils in the periphery are fully
responsive to IL-5 leading to eosinophilia in vivo and to pro-
longed survival in vitro (50), indicating that Btk activation
may be dispensable for IL-5 signaling in eosinophils.
IL-5 enhances gene expression of c-myc, c-fos, c-jun, Cis,
Cish1/Jab and pim-1 at least in activated B cells (51). The
membrane-distal region of bc is involved in the G1to S tran-
sition that is required for the activation of Ras, Raf-1 and
MAPK as well as transcription of c-fos and c-jun but not for
pim-1 and c-myc (12). The membrane-proximal region of bc
is important for cellular proliferation and induction of pim-1
and c-myc (11). Thus, activation of the Ras–MAPK pathway
together with transcription of pim-1, c-myc, c-fos and c-jun
are indispensable for IL-5-induced expansion of eosinophils.
This signaling pathway is further divided into two: one is
JAK–STAT dependent and leads to induction of pim-1 and
the other is JAK–STAT independent and leads to induction
of c-myc (52). Thus, activation of the Ras–MAPK pathway
together with transcription of pim-1, c-myc, c-fos and c-jun
appears to be responsible for IL-5-induced expansion of
Differentiation of EoPs
Despite of possible involvement of IL-5 in eosinophil devel-
opment, the most primitive committed EoPs and the role of
IL-5 in their fate decision have yet to be defined until
recently. GATA-1, a transcription factor expressed in eosino-
phils, has been speculated to play a role in the development
of eosinophils since mice with targeted disruption of the
double GATA motif within the GATA-1 locus show complete
loss of eosinophils (53). Iwasaki et al. (54) have identified
the most primitive committed EoPs in the mouse bone
marrow granulocyte/monocyte progenitors (GMPs).
Of interest, these EoPs are Lin?Sca-1?CD34+c-Kitlo
blastic cells, express IL-5Ra and respond to IL-5 alone or
Slf (steel factor), IL-3, IL-5, IL-9, GM-CSF, erythropoietin and
thrombopoietin, leading them to differentiate exclusively into
eosinophils (54). However, enforced expression of IL-5Ra in
GMPs does not increase the frequency of EoPs, suggesting
that IL-5 does promote proliferation and differentiation of
eosinophilsbut does notpromoteeosinophil lineage
IL-5 in allergic inflammation 1305
by guest on June 8, 2013
commitment. This is consistent with a report in which ectopic
expression of IL-5Ra in bone marrow cells does not increase
the frequency of eosinophil colony formation in the presence
of IL-5 (55, 56). Thus, expression of IL-5Ra on EoPs is a con-
sequence of eosinophil lineage commitment.
In the fetal liver, we identified two classes of IL-5Ra-
positive cell populations. One of them has B-1 cell progeni-
tor potential and expresses IL-5Ra at very low levels; the
other one possesses EoP potential and expresses high lev-
els of IL-5Ra (23, 57). Thus, this picture seems to be also
applicable to fetal hematopoiesis (Fig. 2).
The next question is how lineage commitment to EoPs is
regulated. Nagai et al. (58) reported that Toll-like receptors
are readily expressed on HSCs and their signaling facilitates
myeloid cell lineage differentiation. If innate immune signal-
ings that induce EoPs exist, pathogen itself would be
considered as candidate regulator of eosinophil lineage
commitment. Elucidation of precise mechanisms of eosino-
phil lineage commitment will contribute to the development
ofbrand-new therapeutic drugs
diseases such as asthma.
Survival and function of mature eosinophils
Regarding eosinophil migration from the differentiation site,
i.e. bone marrow, to the bloodstream and eventually to
effecter sites, IL-5 also accelerates this step in an adhesion
molecule (CD11b/CD18; aM/b2 integrin or Mac-1)-dependent
manner (59). IL-5 induces this b2-integrin-mediated adhe-
sion via the PI3K–protein kinase Cd–MAPK pathway (60).
IL-5 also increases eosinophil numbers in the blood and
tissue by inhibiting apoptosis (61, 62). Recently, it was
revealed that mice deficient for proapoptotic protein Bid
(BH3-interacting domain death agonist) had increased eo-
sinophil numbers in the bronchoalveolar lavage (BAL) after
antigen challenge and that those eosinophils were resistant
to FAS-induced apoptosis (63). Although production of Th2
cytokines, including IL-5, is increased in these mice, IL-5
may directly inhibit eosinophil apoptosis via inactivation of
Bid since IL-5 has been reported to block Bid activation
in vitro (64). Effector functions of eosinophils include genera-
tion of reactive oxygen species and secretion of cytotoxic
proteins by degranulation. IL-5 also regulates these steps
via activation of Raf-1 kinase (41) (Fig. 1).
IL-5 and eosinophil-mediated inflammation
The expression of IL-5 mRNA in bronchial biopsies of asth-
matic patients is increased as compared with healthy volun-
teers and the predominant source of IL-5 mRNA is CD4+
T cells (65). Indeed, CD4+T-cell activation in asthma is ac-
companied by increased serum concentrations of IL-5 (66).
IL-5 mRNA and protein are also found in mast cells located
within allergen-challenged tissues. Based on these observa-
tions, an attractive paradigm for eosinophil involvement in
the LAR is as follows: (i) there is up-regulation of IL-5 synthe-
sis by mast cells activated in an immediate hypersensitivity
allergic reaction; this results in (ii) eosinophil recruitment
and activation (67); concomitantly, (iii) CD4+T cells are
recruited by other inflammatory mediators of the allergic re-
action and undergo antigen-specific activation and acquisi-
tion of the Th2 phenotype; this (iv) further enhances
eosinophil recruitment and activation.
It is obvious that eosinophils are involved in the pathology of
asthma because massive eosinophil infiltration is observed in
the airway of asthma patients (68). In asthmatic patients, eosi-
nophils have been detected in high numbers in peripheral
blood, in bronchial mucosa and in the BAL fluid after allergen
challenge (69, 70). IL-5 levels are also elevated in the serum
and the BAL fluid (65). As already mentioned, the expression
of IL-5 mRNA in bronchial biopsy specimens is increased in
asthmatic patients as compared with healthy volunteers. Inha-
lation of recombinant human IL-5 by asthma patients resulted
in increased eosinophil number in the sputum, bronchial
hyper-reactivity and release of eosinophil cationic protein,
suggesting IL-5 as a critical factor for asthma (72).
Animal models further support a role for IL-5 in the
induction of eosinophil-mediated inflammation in allergies
and asthma. IL-5-transgenic mice that express IL-5 in lung
goblet cell hyperplasia, epithelial hypertrophy and airway
hyper-responsiveness (73). A pivotal role for IL-5 in the LAR
has been confirmed by the capacity of neutralizing anti-IL-5
mAb to inhibit antigen-induced or virus-induced airway
airways of mice and guinea pigs (74–76).
In the case of mouse models, results are somewhat
controversial. Administration of anti-IL-5 neutralizing anti-
body or soluble IL-5Ra to sensitized BALB/c mice inhibits
hyper-eosinophilia induced by antigen challenge, but does
not alter bronchial hyper-reactivity (77). In contrast, target
disruption of IL-5 or IL-5Ra in the mice in C57BL/6 back-
and bronchial hyper-reactivity (78, 71). Thus, it is of great in-
terest to test whether IL-5 is a major player in the pathology
of asthma in humans and whether neutralization of IL-5
could be a cure for the disease.
ofeosinophilsas well as
infiltration in the
Eosinophilia is associated with a wide variety of conditions,
including asthma and atopic diseases, helminth infections,
drug hypersensitivity and neoplastic disorders. Early case
reports and treatment of small cohorts of patients who have
eosinophilia using anti-IL-5 mAbs—either mepolizumab or
reslizumab/SCH55700—showed promising results. Results
of humanized anti-IL-5 blocking mAb treatment in patients with
mild asthma confirmed the importance of IL-5 in eosinophil-
mediated inflammation in human (79, 80). Although patients
given a single injection of anti-IL-5 antibody were protected
from allergen-induced blood and sputum hyper-eosinophilia,
they were not protected from allergen-induced LAR or airway
hyper-responsiveness (79), suggesting that airway hyper-
responsiveness occurs independently of IL-5 and airway
eosinophilia. However, recently it was reported that long-term
anti-IL-5 antibody treatment reduces incidence of exacerba-
tion (81, 82). Since symptoms and lung function were still not
improved in the long-term treatment (83), it is suggested that
in humans IL-5 is rather responsive to airway eosinophil-
mediated inflammation, which is closely related with asthma
1306IL-5 in allergic inflammation
by guest on June 8, 2013
Recently, the role of IL-5 and eosinophils in the develop-
ment of airway remodeling, in an experimental model of
chronic asthma, has been carefully studied by using mice
lacking IL-5Ra or mice transgenic for IL-5 (84). The study
has demonstrated that IL-5 plays an obligatory role in the
airway remodeling observed in experimental asthma. Intrigu-
ingly, treatment of wild-type mice with anti-IL-5 antibody
almost completely prevented subepithelial and peribronchial
fibrosis caused by antigen inhalation. Importantly, anti-IL-5
antibody treatment has also been shown to improve airway
remodeling in asthmatic patients (29, 85). Further studies
are required to define the mechanism underlying IL-5- and
eosinophil-mediated airway remodeling in asthma. In mouse
model, administration of anti-IL-5 mAb decreases the
number and cell size of B-1 cells (4). However, functional
impairment of certain B-cell subset after anti-IL-5 treatment
in humans has not been investigated, possibly because def-
inition of human B-1 cell has not been established yet.
Anti-IL-5 therapy has been shown to be effective in patients
with hyper-eosinophilic syndromes (HES), who exhibit diverse
manifestations involving lungs, heart, skin and gastrointestinal
tract. A multicenter, randomized, international, double-blind,
placebo-controlled trial of mepolizumab for the treatment of
HES confirmed the safety and efficacy of anti-IL-5 therapy for
the treatment of HES and provided the first example of suc-
cessful therapy targeting eosinophils in eosinophil-mediated
disorders (86). In these studies, the effect of mepolizumab on
HES patients who were negative for the fusion gene FIP1L1–
PDGFRA (FIP1-like 1–platelet-derived growth factor receptor a)
was evaluated. The authors showed that mepolizumab treat-
ment enabled clinically significant reductions in corticosteroid
dose, and often corticosteroid discontinuation, in HES patients
without major safety concerns.
Koike et al. generated mAbs directed against hIL-5Ra and
characterized their antibody-dependent cell-mediated cyto-
toxicity (ADCC) function using hIL-5Ra-bearing cells. They
reported that one of the mAb (KM1259) markedly inhibited
activities associated with hIL-5/hIL-5R. Humanized versions
of KM1259 created by complementarity-determining region
grafting technology also showed potent inhibitory activity
equivalent to the mouse mAb (87). They also reported
their preliminary data showing that a humanized fucose-
negative mAb (BIW-8405)—generated by POTELLIGENT?
technology—exerted a potent ADCC activity for human eosi-
nophils in the absence of degranulation and release of toxic
granule proteins from eosinophils (88).
Busse et al. (89) assessed the safety and biological activ-
ity of MEDI-563 (known as BIW-8405), a humanized afucosy-
lated IgG1 anti-hIL-5Ra mAb. MEDI-563 neutralizes IL-5
activity and depletes tissue eosinophils in pre-clinical
models and has an acceptable toxicological profile. They
reported that MEDI-563 was well tolerated and no serious
adverse events were observed. Furthermore, circulating eo-
sinophil numbers decreased below detection limits within
24–48 h of dosing in all subjects and the effect lasted for
8–12 weeks post-dosing.
There is overwhelming evidence to support a major role for
Th2 cells and their products such as IL-4, IL-5, IL-9, IL-13,
IL-25 and IL-31 in causing allergic inflammation. Among
these cytokines, IL-5 has pleiotropic effects on various target
cells, including eosinophils and B cells, and induces cell
proliferation, survival and differentiation. Although anti-IL-5
antibody therapy for asthmatic patients still remains elusive,
a potential of humanized anti-human anti-hIL-5Ra mAb treat-
ment for asthmatic patients would be beneficial to eliminate,
by ADCC, eosinophils and basophils localized in the inflam-
matory tissues. The structural, functional and clinical studies
described herein and in future provide insight into the role
of IL-5 in the immune response and control of inflammatory
Grant-in-Aid for Scientific Research on Priority Area from the
Ministry of Education, Science, Sports and Culture, in Japan
(17013024); Grant-in-Aid for Scientific Research (S) from
Japan Society for the Promotion of Science (16109004).
We thank all of the collaborators for their tremendous contribution,
sharing data and helpful discussion. The authors have no conflicting
antibody-dependent cell-mediated cytotoxicity
BH3-interacting domain death agonist
Bruton agammaglobulinemia tyrosine kinase
common cytokine b-chain
extracellular signal-regulated kinase
granulocyte/macrophage colony-stimulating factor
human IL-5 receptor alpha chain
hematopoietic stem cell
IL-5 receptor alpha chain
late-phase allergic response
mitogen-activated protein kinase
v-raf-1 murine leukemia viral oncogene homolog 1
regulatory factor X
Src-homology-2-domain-containing protein tyrosine
phosphoprotein homology 1 domain-containing 1
signal transducer and activator of transcription
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