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The oral cavity serves as the primary path through which substances from the outside world enter our body. Therefore, it functions as a critical component of host defense. Saliva is essential for maintaining a stable oral environment by catching harmful agents, including pathogens, allergens, and chemicals, in the air or food. CCL28, highly expressed in mucosal tissues, such as the colon and salivary glands, is a chemokine that attracts CCR10/CCR3 expressing cells. However, the role of CCL28 in salivary gland formation remains unclear. In this study, we investigated the salivary gland structure in CCL28-deficient mice. Histological analysis showed decreased staining intensity of Alcian blue, which detects acidic mucous, reduced expression of MUC2, and higher infiltration of gram-positive bacteria in the salivary glands of CCL28-deficient mice. In addition, CCL28-deficient mice contained ectopically MUC2-expressed cells in the ducts and reduced the expression of cytokeratin 18, a marker for ductal cells, within the submandibular glands, resulting in decreased duct numbers. Additionally, the submandibular glands of CCL28-deficient mice showed reduced expression of several stem cell markers. These results suggest that CCL28 regulates saliva production via proper differentiation of salivary gland stem cells and could be a valuable biomarker of salivary gland function.

Recent advances in metagenomic analyses have made it easier to analyze microbiota. The microbiota, a symbiotic community of microorganisms including bacteria, archaea, fungi, and viruses within a specific environment in tissues such as the digestive tract and skin, has a complex relationship with the host. Recent studies have revealed that microbiota composition and balance particularly affect the health of the host and the onset of disease. Influences such as diet, food preferences, and sanitation play crucial roles in microbiota composition. The oral cavity is where the digestive tract directly communicates with the outside. Stable temperature and humidity provide optimal growth environments for many bacteria. However, the oral cavity is a unique environment that is susceptible to pH changes, salinity, food nutrients, and external pathogens. Recent studies have emphasized the importance of the oral microbiota, as changes in bacterial composition and balance could contribute to the development of systemic diseases. This review focuses on saliva, IgA, and fermented foods because they play critical roles in maintaining the oral bacterial environment by regulating its composition and balance. More attention should be paid to the oral microbiota and its regulatory factors in oral and systemic health.

This study assessed the somatosensory evoked potentials (SEPs) in dogs and cats to compare the effect of remifentanil on the action potentials evoked by peripheral noxious stimulation in the spinal cord. Five healthy dogs and five healthy cats underwent general anaesthesia induced with propofol and maintained with isoflurane. Each animals received all dosage of a constant-rate infusion of remifentanil at 0 (control), 0.25, 0.5, 1.0 or 2.0 μg/kg/min. The hair of the dorsal foot of a hind limb was clipped and an intraepidermal stimulation electrode that could selectively stimulate the nociceptive Aδ and C fibres was attached. An electrical stimulus was generated by a portable peripheral nerve testing device. The evoked potentials were recorded by two needle electrodes inserted subcutaneously in the dorsal midline between the lumbar vertebra: L3-L4 and L4-L5. Bimodal waveforms were obtained by electrical stimulation in control dogs and cats. The inhibitory effect of remifentanil was evaluated by comparing the changes in the N1P2 and P2N2 amplitudes. The N1P2 amplitude was depressed by remifentanil in a dose-dependent manner in dogs, but it showed no remifentanil-induced changes in cats. While the P2N2 amplitude was also depressed in a dose-dependent manner in dogs, it showed milder remifentanil-induced effects in cats. The N1P2 and P2N2 amplitudes observed herein are assumed to represent the evoked potentials derived from the Aδ and C fibres, respectively. Thus, the inhibitory effect of remifentanil on nociceptive transmission at the spinal cord was much weaker in cats, especially for transmissions possibly derived from Aδ fibres., Competing Interests: Declaration of Competing Interest None of the authors has any financial or personal relationships that could inappropriately influence or bias the content of the paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Oral functions are diverse and critical to human health. Therefore, insufficient secretion or poor quality of saliva, which is secreted into the oral cavity and plays various roles, could have a crucial influence on the oral microenvironment and be associated with systemic disease development. Here, we investigated the effects of food ingredients on saliva quantity and quality, including fermented ones. Through the in vitro submandibular glands' organ culture analyses, we found that "Yomo gyutto," fermented Japanese mugwort (Artemisia princeps), altered the expression of aquaporin-5, a water channel protein. We also found that Yomo gyutto increased saliva volume, along with the amount of α-amylase in mice, and caused changes in the oral microbiome composition of mice. These results suggested that by ingesting Yomo gyutto, we could directly and effectively manipulate the quantity and quality of saliva secreted from the salivary glands, potentially altering the oral microbiome composition for individual health., (© The Author(s) 2022. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Malignant features such as the acquisition of metastatic ability, stemness of cells, and therapeutic resistance of cancer cells are associated with epithelial-mesenchymal transition (EMT) accompanied by changes in motility and morphology. Recent reports implicated that the formation of polyploid giant cancer cells (PGCCs) in human malignancy correlated with the EMT processes. Chemokines are often involved in the regulation of cancer cell migration into tissues, and various types of human cancers exhibit enhanced expression of chemokine receptors, which could augment intrinsic potentials such as invasive activity, proliferating ability, and survival capacity in cancer cells. Nevertheless, the contribution of CCR3 in malignant cancer cells is controversial because it is a well-known primal receptor for the migration of eosinophils, one of the cells of the innate immune system. Here, we explored the blockage of chemokine receptor CCR3 in carcinoma cell lines and found that inhibition of CCR3 induced the formation of polyploid giant cells and stabilization of β-catenin via the PI3K/Akt/GSK-3β signaling pathway, which are processes associated with EMT. As a result of CCR3 inhibition, converted cells acquired enhanced mobile and proliferation abilities. In summary, these data indicate that modulation of the CCR3/PI3K/Akt/GSK-3β signaling pathway regulates polyploidization associated with the EMT processes., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

T helper 17 (Th17) cells express CC chemokine receptor 4 (CCR4) and secrete cytokines such as interleukin-17A (IL-17A) and granulocyte macrophage colony-stimulating factor (GM-CSF), while dendritic cells (DCs) produce CC chemokine ligand 22 (CCL22), a CCR4 ligand, upon stimulation with GM-CSF. Th17 cells are known to play a critical role in the pathogenesis of rheumatoid arthritis (RA). CCL22 has also been shown to be up-regulated in the synovial tissues of RA patients. Here, we investigated the role of CCR4 in collagen-induced arthritis (CIA), a mouse model of RA. DBA/1J mice efficiently developed CIA as shown by erythema, paw swelling, joint rigidity, and joint destruction. Th17 cells were increased in the arthritic joints and regional lymph nodes (LNs) of CIA mice. A fraction of Th17 cells were also shown to produce GM-CSF. On the other hand, we observed no significant increases of Th2 cells or Treg cells, the T cell subsets also known to express CCR4, in these tissues. We further observed clusters of CCR4-expressing memory Th17 cells and CCL22-producing DCs in the regional LNs of CIA mice, supporting the role of the CCR4-CCL22 axis in the expansion of Th17 cells in the regional LNs. Compound 22, a CCR4 inhibitor, ameliorated the disease severity with reduction of Th17 cells in the arthritic joints and regional LNs and Th17-DC clusters in the regional LNs. We further confirmed that CCR4-deficient mice in the C57BL/6J background were highly resistant to CIA induction compared with wild-type mice. Collectively, CCR4 contributes to the pathogenesis of CIA and may thus represent a new therapeutic target for RA., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Japanese Society for Immunology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The development of the parathyroid and the thymus from the third pharyngeal pouch depends on the activities of the Gcm2 and Foxn1 transcription factors, respectively, whose expression domains sharply demarcate two regions in the developing third pharyngeal pouch. Here, we have generated novel mouse models to examine whether ectopic co-expression of Gcm2 in the thymic epithelium and of Foxn1 in the parathyroid perturbs the establishment of organ fates in vivo. Expression of Gcm2 in the thymic rudiment does not activate a parathyroid-specific expression programme, even in the absence of Foxn1 activity. Co-expression of Foxn1 in the parathyroid fails to impose thymopoietic capacity. We conclude that the actions of Foxn1 and Gcm2 transcription factors are cell context-dependent and that they each require permissive transcription factor landscapes in order to successfully interfere with organ-specific cell fate., (© 2022. The Author(s).)

Psoriasis is a chronic skin disease associated with T helper (Th)17-mediated inflammation. Because CCR4 is a major chemokine receptor expressed on Th17 cells, we investigated the role of CCR4 in a modified imiquimod-induced psoriasis model that showed enhanced skin infiltration of Th17 cells. CCR4-deficient mice had less severe skin disease than wild-type mice. Th17 cells were decreased in the skin lesions and regional lymph nodes of CCR4-deficient mice. In the regional lymph nodes of wild-type mice, CD44 + memory Th17 cells expressing CCR4 were found to be clustered with dendritic cells expressing CCL22, a ligand for CCR4. Such dendritic cell‒Th17 cell clusters were significantly decreased in CCR4-deficient mice. Similar results were obtained using the IL-23‒induced psoriasis model. In vitro, compound 22, a CCR4 antagonist, significantly reduced the expansion of Th17 cells in the coculture of CD11c + dendritic cells and CD4 + T cells separately prepared from the regional lymph nodes of wild-type mice with psoriasis. In vivo, compound 22 ameliorated the psoriasis-like skin disease in wild-type mice with significant decreases of Th17 cells in the regional lymph nodes and skin lesions. Collectively, CCR4 is likely to play a role in the pathogenesis of psoriasis through the expansion of Th17 cells., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Exposure to moderate doses of ionizing radiation (IR), which is sufficient for causing skin injury, can occur during radiation therapy as well as in radiation accidents. Radiation-induced skin injury occasionally recovers, although its underlying mechanism remains unclear. Moderate-dose IR is frequently utilized for bone marrow transplantation in mice; therefore, this mouse model can help understand the mechanism. We had previously reported that bone marrow-derived cells (BMDCs) migrate to the epidermis-dermis junction in response to IR, although their role remains unknown. Here, we investigated the role of BMDCs in radiation-induced skin injury in BMT mice and observed that BMDCs contributed to skin recovery after IR-induced barrier dysfunction. One of the important mechanisms involved the action of CCL17 secreted by BMDCs on irradiated basal cells, leading to accelerated proliferation and recovery of apoptosis caused by IR. Our findings suggest that BMDCs are key players in IR-induced skin injury recovery.

The onset of lymphocyte development in the vertebrate primordial thymus, about 500 million years ago, represents one of the foundational events of the emerging adaptive immune system. Here, we retrace the evolutionary trajectory of thymopoiesis, from early vertebrates to mammals, guided by members of the Foxn1/4 transcription factor gene family, which direct the differentiation of the thymic microenvironment. Molecular engineering in transgenic mice recapitulated a gene duplication event, exon replacements, and altered expression patterns. These changes predictably modified the lymphopoietic characteristics of the thymus, identifying molecular features contributing to conversion of a primordial bipotent lymphoid organ to a tissue specializing in T cell development. The phylogenetic reconstruction associates increasing efficiency of T cell generation with diminishing B cell-generating capacity of the thymus during jawed vertebrate evolution., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Neutrophils are important phagocytic cells for host defense against pathogens. They are rapidly recruited to the site of infection, release antimicrobial peptides and cytokines, and engulf and kill microbes. Neutrophils also accumulate in allergic inflammatory sites. Here we characterized neutrophil accumulation in the nasal mucosa using a mouse model of allergic rhinitis, in which mice were sensitized by intraperitoneal injection of ovalbumin (OVA) and then challenged by intranasal administration of OVA or PBS. In the nasal mucosa of both PBS- and OVA-challenged mice, we found a cell subset expressing the eosinophil marker Siglec-F in the Ly-6G + neutrophil population. Morphological analysis of the sorted Ly-6G + Siglec-F + cells revealed that they were devoid of eosinophilic granules in the cytosol and were apparently neutrophils, but compared to conventional Ly-6G + Siglec-F - neutrophils, they had a more lobulated, "botryoid" nucleus. Siglec-F + neutrophils were barely found in the nasopharynx-associated lymphoid tissue, cervical lymph nodes, the spleen, or blood. Both Siglec-F + neutrophils and conventional neutrophils showed increased numbers in the nasal mucosa of OVA-challenged mice. Compared to conventional Siglec-F - neutrophils, Siglec-F + neutrophils exhibited an activated phenotype and enhanced effector functions. Taken together, our findings identify Siglec-F + neutrophils as a novel neutrophil subset with an activated phenotype that resides specifically in the nasal mucosa., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Atopic dermatitis is a chronic inflammatory skin disease involving T-helper (Th) 2 cells, eosinophils, and mast cells. Although CCR4 is a major chemokine receptor expressed on Th2 cells and regarded as a potential therapeutic target for allergic diseases, its role in atopic dermatitis remains unclear. Here, by using a hydrogel patch as a transcutaneous delivery device for ovalbumin (an antigen) and Staphylococcus aureus δ-toxin (a mast cell activator), we efficiently induced acute atopic dermatitis-like skin lesions in BALB/c mice, a strain prone to Th2 responses, which were characterized by increased numbers of eosinophils, mast cells, and CCR4-expressing Th2 cells in the skin lesions; elevated levels of total and ovalbumin-specific IgE in the sera; and increased expression of IL-4, IL-17A, IL-22, CCL17, CCL22, and CCR4 in the skin lesions. Of note, the same model was less efficient in C57BL/6 mice, a strain prone to Th1 responses. Using this atopic dermatitis model in BALB/c mice, we demonstrated that CCR4-deficiency or a CCR4 antagonist ameliorated the allergic responses. Collectively, these results demonstrate that CCR4 plays a pivotal role in skin allergic inflammation of BALB/c mice by recruiting CCR4-expressing Th2 cells and Th17 cells., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

The numbers of thymic epithelial cells (TECs) and thymocytes steadily increase during embryogenesis. To examine this dynamic, we generated several TEC-specific transgenic mouse lines, which express fluorescent proteins in the nucleus, the cytosol and in the membranes under the control of the Foxn1 promoter. These tools enabled us to determine TEC numbers in tissue sections by confocal fluorescent microscopy, and in the intact organ by light-sheet microscopy. Compared to histological procedures, flow cytometric analysis of thymic cellularity is shown to underestimate the numbers of TECs by one order of magnitude; using enzymatic digestion of thymic tissue, the loss of cortical TECs (cTECs) is several fold greater than that of medullary TECs (mTECs), although different cTEC subsets appear to be still present in the final preparation. Novel reporter lines driven by Psmb11 and Prss16 promoters revealed the trajectory of differentiation of cTEC-like cells, and, owing to the additional facility of conditional cell ablation, allowed us to follow the recovery of such cells after their depletion during embryogenesis. Multiparametric histological analyses indicate that the new transgenic reporter lines not only reveal the unique morphologies of different TEC subsets, but are also conducive to the analysis of the complex cellular interactions in the thymus.

CCR4 is a major chemokine receptor expressed by Treg cells that downregulate immune responses. Here, we investigated the role of CCR4-mediated Treg cell recruitment in antigen-specific immune responses. CCR4-deficient mice immunized intramuscularly with ovalbumin (OVA) showed enhanced OVA-specific IgG responses. Furthermore, intramuscular administration of OVA induced the expression of MDC/CCL22, a ligand for CCR4, in macrophages of the muscle tissues, and enhanced the recruitment of CCR4+ Treg cells in wild-type mice, whereas this recruitment of Treg cells was severely impaired in CCR4-deficient mice. Furthermore, OVA-loaded dendritic cells (DCs) derived from the muscle injection site of CCR4-deficient mice had an upregulated expression of the DC activation marker CD40 and 86, and the lymphoid organ homing receptor CCR7 resulting in an increased number of migratory DCs in the regional lymph node. Compound 22, a CCR4 antagonist, also inhibited the recruitment of Treg cells to the muscle tissue, and further enhanced DC activation and homing to the regional lymph node. Consequently, Compound 22 enhanced OVA-specific IgG responses, and the expression levels of IL-4 and IFN-γ in CD4+ T cells and the levels of IFN-γ in CD8+ T cells. Finally, intramuscular administration of OVA and Compound 22 significantly inhibited the growth of OVA-expressing tumors. Collectively, CCR4 plays a pivotal role in Treg cell recruitment to the muscle tissue, and intramuscular administration of CCR4 antagonists may be a promising approach for enhancing vaccine efficacy., (Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

CCL28 induces the migration of IgA Ab-secreting cells (ASCs) via CCR10 and also displays a potent antimicrobial activity in vitro. To explore the role of CCL28 in vivo, we generated CCL28-deficient mice. The mice exhibited a significant reduction and abnormal distribution of IgA ASCs in the lamina propria of the colon. The concentrations of total and Ag-specific IgA in the fecal extracts of CCL28-deficient mice were also drastically reduced. The average amount of IgA secreted by a single IgA ASC derived from the colon was also substantially reduced in CCL28-deficient mice. Furthermore, CCL28 was found to significantly increase the average amount of IgA secreted by a single IgA ASC derived from the colon in vitro. In contrast, the generation of IgA ASCs in Peyer's and cecal patches was not significantly impaired in CCL28-deficient mice. We also found a relative increase in the Class Bacilli in the fecal extracts of CCL28-deficient mice and demonstrated a potent antimicrobial activity of CCL28 against Bacillus cereus and Enterococcus faecalis, both of which belong to Class Bacilli. Thus, CCL28 may also suppress the outgrowth of some bacterial species by its direct antimicrobial activity. Finally, CCL28-deficient mice exhibited a highly aggravated dextran sodium sulfate-induced colitis that was ameliorated by pretreatment with antibiotics. Collectively, CCL28 plays a pivotal role in the homing, distribution, and function of IgA ASCs in the colon and may also affect the intestinal microbiota through its direct antimicrobial activity., (Copyright © 2018 by The American Association of Immunologists, Inc.)

The ezrin-radixin-moesin (ERM) proteins are a family of membrane-associated proteins that link membrane proteins with actin filaments in the cell cortex and regulate many cellular processes, including cell shape determination, membrane transport, and signal transduction. Lymphocytes predominantly express two ERM members, ezrin and moesin. Mutations in the moesin gene in humans are associated with primary immunodeficiency with profound lymphopenia, and moesin-deficient mice exhibit a similar lymphopenia phenotype. In this study, we show that aging moesin-deficient mice develop a systemic lupus erythematosus-like autoimmune phenotype, which is characterized by elevated serum autoantibody levels and glomerulonephritis. Younger moesin-deficient mice exhibited elevated basal levels of several Ig isotypes and enhanced Ab affinity maturation upon immunization. Germinal center B cells and follicular helper T cells spontaneously accumulated in unimmunized mice, and CD8 + CD44 + CD122 + Ly49 + regulatory T (CD8 + Tregs) cells, which inhibit the expansion of follicular helper T cells, were severely reduced in these mice. Isolated CD8 + Treg cells from moesin-deficient mice showed impaired proliferation in response to IL-15, which was accompanied by defects in STAT5 activation and IL-15Rα internalization, suggesting that moesin plays a key role in IL-15-mediated signaling. These findings underscore the importance of moesin in IL-15-dependent CD8 + Treg cell homeostasis and, thus, the control of self-tolerance., (Copyright © 2017 by The American Association of Immunologists, Inc.)

This study was conducted to identify the brain regions corresponding to mechanical noxious stimulation in cats using functional magnetic resonance imaging (fMRI) and to investigate the modulatory effect of remifentanil on the activation of these regions. Six healthy cats were anesthetized using a constant-rate infusion of alfaxalone. Cats were allocated to one of three treatment groups: remifentanil 0 (saline), 0.25, and 0.5μg/kg/min. A 3.0-T MRI unit was used to collect fMRI data. During the fMRI scanning, mechanical noxious stimulation was applied by tail clamping. The brain regions activated by the stimulation were identified based on blood oxygenation level-dependent (BOLD) responses. The modulatory effects of remifentanil were evaluated using a region of interest (ROI) analysis comparing signal changes in each brain region. Increased activity from noxious stimulation was observed in the somatosensory area (the postcruciatus gyrus, the anterior part of the marginalis gyrus, and the anterior part of the ectomarginalis gyrus), the parietal association area (the middle part of the marginalis gyrus and the middle part of the ectomarginalis gyrus), the cingulate cortex, the hippocampus, and the cerebellum. The results of the ROI analysis indicated that activations in the somatosensory area, the cingulate cortex, the hippocampus, and the cerebellum were significantly modulated (P<0.05) by remifentanil. In cats, activation patterns evoked by mechanical noxious stimulation were observed in several brain regions thought to be involved in various aspects of pain processing, including sensory discrimination and integration, affect, and motor response. These brain responses were modulated by remifentanil., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The thymus is the site of T cell development in vertebrates. In general, the output of T cells is determined by the number of thymic epithelial cells (TECs) and their relative thymopoietic activity. Here, we show that the thymopoietic activity of TECs differs dramatically between individual mouse strains. Moreover, in males of some strains, TECs perform better on a per cell basis than their counterparts in females; in other strains, this situation is reversed. Genetic crosses indicate that TEC numbers and thymopoietic capacity are independently controlled. Long-term analysis of functional parameters of TECs after castration provides evidence that the number of Foxn1-expressing TECs directly correlates with thymopoietic activity. Our study highlights potential complications that can arise when comparing parameters of TEC biology across different genetic backgrounds; these could affect the interpretation of the outcomes of interventions aimed at modulating thymic activity in genetically diverse populations, such as humans.

Autoimmune and inflammatory conditions are frequent complications in patients with reduced numbers of T cells. Here, we describe a mouse model of thymic stromal dysplasia resulting in peripheral T-cell lymphopenia. In Foxn1:CFP-NTR transgenic mice, the bacterial nitroreductase enzyme is expressed in thymic epithelial cells and converts the prodrug CB1954 into a cytotoxic agent. This strategy enables titratable and durable destruction of thymopoietic tissue in early embryogenesis. Our results indicate that the resulting low levels of thymic capacity for T-cell production create a predisposition for the development of a complex autoimmune syndrome, chiefly characterized by inflammatory bowel disease and lymphocytic organ infiltrations. We conclude that the Foxn1:CFP-NTR transgenic mouse strain represents a suitable animal model to optimize established clinical protocols, such as thymus transplantation, to correct various forms of thymic dysplasia and to explore novel treatment options., (© The Author 2017. Published by Oxford University Press on behalf of The Japanese Society for Immunology.)

Obesity and type 2 diabetes mellitus (T2DM) are occurring at epidemic-like rates, and these epidemics appear to have emerged largely from changes in daily diet. In the present study, we compared effects of high-fat diet (HFD) and fructose-rich diet (FRD) in WBN/Kob-Lepr fa (WBKDF) rats that spontaneously develop obesity, dyslipidemia and T2DM. After a 4-week feeding of each diet, WBKDF-HFD and WBKDF-FRD rats exhibited aggravated obesity and dyslipidemia compared with WBKDF rats fed standard diet (STD). In contrast, hyperglycemia developed in WBKDF-STD rats was significantly inhibited in WBKDF-FRD rats, but not in WBKDF-HFD rats. The present study demonstrated that the 4-week feeding of HFD and FRD caused diet-induced obesity with a distinct phenotype in the glucose metabolism in WBKDF rats.

During nasal immune responses, lymphocytes activated in the nasopharynx-associated lymphoid tissue (NALT) are thought to traffic to the nasal mucosa. Here we found a prominent infiltration of CD4(+) memory T cells into the nasal mucosa in a mouse model of allergic rhinitis. CCR3 and CCR10 mRNA was increased in the NALT, and CCR3- or CCR10-expressing CD4(+) T cells were present in the nasal mucosa. CCL28, a chemokine ligand for CCR3 and CCR10, was upregulated in nasal epithelial cells. Our results suggest that memory CD4(+) T cells traffic to the nasal mucosa in a process that may involve CCL28 and its receptors CCR3 and CCR10., (Copyright © 2016 Elsevier Inc. All rights reserved.)