Role Of Thymic Stromal Lymphopoietin Research Articles

Thymic stromal lymphopoietin: Next research hotspot of carcinogenesis?

Thymic stromal lymphopoietin (TSLP) is an epithetlial cell derived cytokine which has been reported to be a master regulator in T helper (Th) 2 driven inflammation. Through acting on dentritic cells (DCs), granulocytes, natural killer T cells or directly on CD4+ T cells, TSLP plays significant roles in the pathogenesis of atopic diseases consisting of the triad of asthma, allergic rhinitis and atopic dermatitis. Recently mounting evidence demonstrated that cancer-related inflammation play decisive roles at different stages of tumor development, including initiation, promotion, malignant conversion, invasion, and metastasis. As a crucial regulator of Th2 driven inflammation, the involvement of TSLP in carcinogenesis have attracted researchers’ attention. However, the mechanisms of TSLP’s involvement in carcinogenesis are still largely unknown. In this review we first outline the roles of TSLP involved in allergic inflammation and then we further focus on the recent findings on TSLP’s tumor promoting activities hoping to provide hints on elucidation of the TSLP implication in carcinogenesis in future studies.

The Role of TSLP in IL-13-Induced Atopic March

Although atopic dermatitis (AD) is the initial step of the “atopic march”, a progression from AD to asthma, the underlying mechanism remains unknown. Selective expression of IL-13 in the skin of mice caused an AD phenotype resembling human AD, and the disorder was associated with enhanced production of thymic stromal lymphopoietin (TSLP) in the AD skin with a systemic Th2 immunity. Here we show that IL-13 transgenic mice with AD had significantly enhanced lung inflammation, mucus hypersecretion, and airway hyperresponsiveness (AHR) when sensitized and challenged by allergen. In addition, the level of TSLP was significantly higher in acute AD than in chronic AD. Furthermore, elimination of TSLP signaling significantly diminished the allergic asthma responses, immune cell production of Th2 cytokines (IL-4, IL-13), and serum IgE. These studies indicate that IL-13 induces AD and atopic march via a TSLP dependent mechanism.

Critical proinflammatory role of thymic stromal lymphopoietin and its receptor in experimental autoimmune arthritis

The interleukin-7 (IL-7)-related cytokine thymic stromal lymphopoietin (TSLP) is a potent activator of myeloid dendritic cells, enhancing Th2-mediated hypersensitivity, and it has been implicated in the pathogenesis of atopic diseases. Although intraarticular concentrations of TSLP have been shown to be increased in patients with rheumatoid arthritis (RA), the functional capacities of TSLP in arthritis are poorly studied. The purpose of this study was to investigate the effects of TSLP administration and TSLP receptor deficiency on immune activation, arthritis severity, and tissue destruction in T cell-driven arthritis models of RA. Immunopathology was studied in arthritic mice that were given multiple injections of murine recombinant TSLP and in mice that were deficient in the TSLP receptor (TSLPR(-/-)). Arthritis severity and incidence were determined by visual examination of the paws. Joint destruction was determined by assessing radiographs and the immunohistochemistry of ankle joints. Total cellularity and numbers of T cell subsets were assessed. Proinflammatory mediators were measured by multianalyte profiling of serum or paw protein extracts. Administration of TSLP significantly exacerbated the severity of collagen-induced arthritis and the joint damage that was associated with increased T cell activation. Furthermore, TSLPR(-/-) mice had less severe arthritis than did wild-type mice. TSLPR(-/-) mice had diminished concentrations of local proinflammatory and catabolic mediators, including IL-17, IL-1β, IL-6, basic fibroblast growth factor, and matrix metalloproteinase 9, while levels of the regulatory cytokines IL-10 and IL-13 were increased. TSLP and its receptor enhance Th17-driven arthritis and tissue destruction in experimental arthritis. The increased expression of TSLP as well as the increased number of TSLPR-expressing cells in the joints of patients with RA suggest that TSLP and its receptor constitute novel therapeutic targets in RA.

Increased prevalence of regulatory T cells in the lung cancer microenvironment: a role of thymic stromal lymphopoietin.

Expansion of CD4+CD25+ regulatory T cells (Tregs) in tumor microenvironment was one of the mechanisms by which cancer cells escaped host defense. Thymic stromal lymphopoietin (TSLP) contributes to the generation of natural Tregs in thymus. Therefore, the purpose of this report was to investigate the role of TSLP in the increasing prevalence of Tregs in lung cancer microenvironment. The expression ratio of TSLP protein in tumor tissues was significantly increased compared with that in benign lesion and non-cancer lung tissue. The prevalence of Tregs in tumor microenvironment was correlated with the expression of TSLP in lung cancer. Dendritic cells (DCs) were induced from peripheral blood mononuclear cells (PBMCs) collected from lung cancer patients and left unstimulated (imDCs) or exposed to hTSLP (TSLP-DCs) or LPS (LPS-DCs). TSLP-DCs expressed intermediate levels of CD83 and high levels of CD86, CD11C, and HLA-DR, which showed a characteristic of less mature DCs. TSLP-DCs secreted low levels of IL-6, IL-12, IL-10, TNF-α and IFN-γ, and high levels of TGF-β and MDC. The percentage of Tregs in CD4+CD25- T cells cocultured with TSLP-DCs group was statistically higher than that of LPS-DCs and imDCs. Transwell assays showed that TSLP-DCs exhibited increased ability to attract the migration of CD4+CD25- Tregs, when compared with imDCs. These results indicated that TSLP proteins were expressed in lung tumor tissue and correlated with the prevalence of Tregs. TSLP-DCs could induce CD4+CD25- T cells to differentiate into CD4+CD25+foxp3+ T cells and the migration of CD4+CD25+ T cells.

The role of thymic stromal lymphopoietin in the immunopathogenesis of atopic dermatitis

Atopic dermatitis (AD), a skin disease characterized by pruritus and chronic inflammation, results from a complex interplay between environmental and genetic factors. Thymic stromal lymphopoietin (TSLP), an IL-7-like cytokine, is believed to propagate AD lesions through T helper 2 (Th2) polarization. This paper describes the immunologic mechanisms involving TSLP in the generation of allergic disease. Specifically in AD, TSLP has been shown to be an inducer of myeloid dendritic cells, Th2 responses, mast cells, and natural killer T cells, thereby leading to cytokine secretion and the development of AD. We hope that further understanding of the TSLP pathway and its role in the pathogenesis of AD will lead to improved clinical management of AD in the future.

Thymic stromal lymphopoietin and allergic dermatoses

Allergic dermatoses are a group of diseases characterized by Th2 predominance, eosinophilic infiltration and IgE elevation. The imbalance of Th1ATh2 is an important pathogenesis of allergic dermatoses. Thymic stromal lymphopoietin (TSLP) is an interleukin 7-like cytokine, and has attracted a lot of attention for its distinct roles in allergic dermatoses. Up to now, it has been regarded as a general switch or mater regulator in the triggering of Th2-driven inflammation. Here, the authors review the structure of TSLP and its receptor, how TSLP induces Th2 cell responses and the crucial role of TSLP in allergic dermatoses. Key words: Thymic stromal lymphopoietin; Dermatitis, atopic; Allergic; Th2 cells

Thymic stromal lymphopoietin mediates breast cancer progression and metastasis (48.9)

Abstract Breast cancer escape and metastasis is an active process that requires inflammation and participation of immune cells. We have previously reported that this is a primary tumor-controlled process which activates lungs to produce CCL17 and CCL22 to facilitate lung metastasis together with the recruitment of CCR4+ regulatory T cells (Tregs). To understand the mechanism of this process, we performed expression array analysis in both metastatic and non-metastatic cancer cells and found that metastatic cells produced thymic stromal lymphopoietin (TSLP), an IL-7-like type 1 inflammatory cytokine that is often associated with the induction of Th2-type allergic responses in the lungs. Moreover, TSLP was also abundantly expressed in variety of human solid tumors, including breast, lung, colon and ovarian cancers. To gain further insights into the role of TSLP in cancer progression, we have blocked TSLP expression in cancer cells and found that TSLP is required for efficient breast cancer escape and metastasis. Moreover, utilizing adoptive transfer studies in TSLPR deficient mice, we demonstrated that by targeting CD4+ T cells to induce Th2-type inflammatory responses, cancer-produced TSLP promoted cancer escape. Taken together, our data indicate that TSLP is an important factor that needs to be controlled to effectively combat with cancer escape.

Role of Thymic Stromal Lymphopoietin in the Pathogenesis of Nasal Polyposis

IntroductionPolyposis is an end form of chronic mucosal inflammation in a number of disorders and has an important impact on patient’s life quality. Thymic stromal lymphopoietin (TSLP) is involved in many inflammatory processes such as asthma and allergic rhinitis (AR). The aim of this study is to elucidate the role of TSLP in the pathogenesis of polyposis. MethodsNinety-four patients with nasal polyposis (NP) and/or allergic rhinitis (AR) were treated with inferior turbinectomy and polyp resection. Levels of TSLP in the nasal epithelial layer were measured; expression of TSLP receptor and OX40 ligand (OX40L) was assessed in isolated nasal mucosal dendritic cells (DC); tumor necrosis factor (TNF), interleukin (IL)-4 and interferon (IFN)-γ expressions were determined in isolated nasal mucosal CD4+ T cells. ResultsThe levels of TSLP in nasal epithelial layer were higher in the NP group than in the non-NP group. Higher expression of TSLP receptor and OX40L were detected in DCs of NP nasal mucosa. TNF-α+ IL-4+CD4+ T cells were detected in NP/AR nasal mucosa; TNF+ IFN-γ+ CD4+ T cells were identified in NP/non-AR nasal mucosa. TSLP-primed DCs drove naive CD4+ T cells to become TNF+ IL-4+ CD4+ T cells, whereas TSLP/lipopolysaccharide-primed DCs induced naive CD4+ T cells to become TNF+ IFN-γ+ T cells. ConclusionsThe data indicate that TSLP is involved in the pathogenesis of polyposis.

Increased Expression and Role of Thymic Stromal Lymphopoietin in Nasal Polyposis

PurposeNasal polyposis is a chronic inflammatory disease of the upper airways often associated with asthma and characterized by markedly increased numbers of eosinophils, Th2 type lymphocytes, fibroblasts, goblet cells and mast cells. Previous studies have shown elevated levels of thymic stromal lymphopoietin (TSLP) in atopic diseases like asthma, atopic dermatitis and mainly in animal models of allergic rhinitis (AR). Here, we investigated the expression of TSLP in nasal polyps from atopics and non-atopics in comparison with the nasal mucosa and its potential role in nasal polyposis.MethodsMessenger RNA expression for TSLP, thymus and activation-regulated chemokine (TARC) and macrophage derived chemokine (MDC) in nasal polyps and nasal mucosa of atopics and non-atopics was analyzed by real time PCR. Immunoreactivity for TSLP in nasal polyps and in the nasal mucosa of patients with AR and non-allergic rhinitis (NAR) was analyzed by immunohistochemistry. Eosinophil counts was analyzed by Wright-Giemsa staining and nasal polyp tissue IgE, by ELISA.ResultsMessenger RNA expression for TSLP,TARC and MDC was markedly higher in nasal polyps as compared to the allergic nasal mucosa. Immunoreactivity for TSLP was detected in epithelial cells, endothelial cells, fibroblasts and inflammatory cells of the nasal mucosa and nasal polyps. The number of TSLP+ cells was significantly greater in the nasal mucosa of AR than NAR patients. The number of TSLP+ cells in nasal polyps from atopics was significantly greater than that of non-atopics and that in the allergic nasal mucosa. The number of TSLP+ cells correlated well with the number of eosinophils and the levels of IgE in nasal polyps.ConclusionsThe high expression of TSLP in nasal polyps and its strong correlation to eosinophils and IgE suggest a potential role for TSLP in the pathogenesis of nasal polyps by regulating the Th2 type and eosinophilic inflammation.

Role of Thymic Stromal Lymphopoietin (TSLP) in Palifermin-Mediated Immune Modulation and Protection from Acute Murine Graft-Versus-Host Disease

Using the C57BL/6→(C57BL/6 x DBA/2)F(1)-hybrid model of acute graft-versus-host disease (GVHD), we previously showed that treating the donor mice with palifermin provides protection from morbidity and a shift from Th1 to Th2 cytokine production. To determine whether thymic stromal lymphopoietin (TSLP) is involved in palifermin-mediated immune modulation, we used donors from the following groups: (1) untreated wild-type donors, (2) palifermin-treated wild-type donors, (3) untreated TSLPR(-/-) donors, and (4) palifermin-treated TSLPR(-/-) donors. Survival in the recipients was 0%, 100%, 31%, and 0%, for groups 1-4, respectively, indicating that TSLP responsiveness is required for palifermin-mediated protection from GVHD. We also found that the increases in Th2 cytokine levels that are induced by palifermin treatment are obviated in TSLPR(-/-) donors, and that protection from GVHD (group 2) is associated with a higher percentage of CD4(+)CD25(+)Foxp3(+) cells in the graft. Collectively, our findings show that when palifermin and TSLP act in concert, the predominant effect is protection in this model.

Thymic stromal lymphopoietin induces early human B‐cell proliferation and differentiation

Thymic stromal lymphopoietin (TSLP) is a cytokine that binds the IL-7-receptor-alpha chain and a unique TSLP receptor (TSLPR) chain. The role of TSLP in human B-cell development has not been elucidated. We show that TSLPR transcripts are expressed most prominently in CD34(+) cells from fetal liver and BM. In general, cell surface expression of TSLPR was low, except on a subset of multilineage-commited progenitor cells. TSLP induced the tyrosine-phosphorylation of STAT5 and the proliferation of multilineage-commited progenitor cells, pro-B cells and pre-B cells. Compared with IL-7, the levels of proliferation after stimulation of the B-cell progenitors with TSLP were lower. Expression of the BCR on the cell surface of fetal cells was inversely correlated to TSLP or IL-7 responsiveness. Pre-B cells from fetal BM, but not fetal liver, were refractory to TSLP or IL-7 stimulation. When employing an in vitro B-cell differentiation culture system starting from CD34(+)CD38(-) multipotent HSC, IL-7 induced a short wave of precursor cell expansion but did not result in long-term survival of mature B cells. TSLP was capable of increasing the proportion and the absolute numbers of more mature human B cells. Overall, we provide evidence that TSLP supports human B-cell differentiation from fetal hematopoietic progenitors.

Roles of TSLP in diverting airway tolerance to Th2 sensitization (91.6)

Abstract Induction of Foxp3+ regulatory T cells (iTreg) is an important mechanism to generate mucosal tolerance against harmless antigens. On the other hand, mucosal tolerance breakdown is an important step towards allergen sensitization that ultimately leads to allergy and asthma. Recent studies demonstrated that thymic stromal lymphopoietin (TSLP) is essential for the development of allergic inflammation. The precise mechanism by which TSLP induces allergic response remains inadequately understood. Here we report that intranasal treatment of Ovalbumin (OVA) + TSLP was sufficient to induce Th2 sensitization against OVA while inhalation of OVA induced airway tolerance. In fact, elevated airway TSLP was able to suppress the development of antigen-specific iTregs in a dose dependent manner. We further demonstrated that TSLP significantly inhibited the differentiation of Tregs in vitro. This inhibition was TSLP specific as naïve CD4 T cells isolated from TSLP receptor deficient mice showed normal iTreg differentiation in the presence of TSLP. Although TSLP could directly promote Th2 differentiation in vitro, IL-4 or Stat6 deficiency only partially rescued the inhibition of iTreg induction by TSLP. Taken together, our findings suggest that TSLP, in addition to promote Th2 differentiation, can directly suppress antigen-specific iTreg induction in response to inhaled antigens, and thus induces Th2 sensitization and allergic inflammation.

Thymic stromal lymphopoietin is present in human breast milk

Thymic stromal lymphopoietin (TSLP) has emerged as a potential key mediator of both the initiation and maintenance of Th2 responsiveness and thereby the allergic inflammatory cascade. Given the possible role of TSLP in initiating Th2-mediated allergic disease more detailed investigation of TSLP expression and responsiveness in early life is warranted. Therefore, the presence of TSLP in breast milk was evaluated. Defatted human breast milk collected at 3-5 days and 11-26 days postpartum (n=22/group) and commercially available ready-made baby formula (n=3) were analysed for TSLP with a specific ELISA. TSLP was detectable in breast milk but not in commercial ready-made formulas. Levels in breast milk were significantly higher (p<0.001) at 3-5 days than at 11-26 days postpartum. The potential role of breast milk TSLP in the development of immune function within the neonatal gastrointestinal tract and the development of allergy in childhood remain to be determined.

What determines Th2 differentiation, in vitro and in vivo?

We have known since 1991 how to induce naive CD4 T cells to differentiate in vitro into Th2 cells and, over the ensuing years, a comprehensive picture of the molecules involved in this important process has emerged. GATA3 and STAT5 are both essential for in vitro differentiation, stimulating naive cells through a process involving induction, which is T-cell receptor (TCR) dependent but interleukin (IL)-4 independent, and commitment, which is IL-4 dependent. Th2 differentiation in vivo appears more complex. GATA3 and probably STAT5 are required in vivo but, at least for certain helminth infections, the IL-4/IL-4Ra/STAT6 pathway is dispensable. The role of thymic stromal lymphopoietin and of low TCR signal strength and the participation of basophils in establishing a Th2-baising in vivo environment have achieved considerable attention. Here I discuss the major players in Th2 differentiation particularly as they may exert their effects in vivo.

The Role of Thymic Stromal Lymphopoietin in Allergic Inflammation and Chronic Obstructive Pulmonary Disease

Thymic stromal lymphopoietin (TSLP) primes dendritic cells to promote a Th2 inflammatory response. Its action is mediated by a heterodimeric receptor which consists of the interleukin-7 receptor alpha chain and the TSLP receptor chain (TSLPR). TSLPR resembles the common gamma chain subunit utilized by many type 1 cytokine receptors. Normal epithelial cells, keratinocytes, and stromal cells constitutively express TSLP. Dendritic cells that are activated by TSLP promote the development of CD4(+) T cells into pro-inflammatory Th2 cells. TSLP thus plays a potentially important role in the pathogenesis of allergic inflammation in asthma and atopic dermatitis. TSLP also has direct effects on other types of cells in the bronchial mucosa. It is over-expressed in the bronchial mucosa in chronic obstructive pulmonary disease (COPD), which is traditionally described as a Th1-related disease, as well as severe asthma, which is traditionally described as a Th2-related disease. In this review we will discuss TSLP expression, function, and available and potential mechanisms in both allergic inflammation and COPD.

TSLP and Downstream Molecules in Experimental Mouse Allergic Conjunctivitis

To explore the potential role of thymic stromal lymphopoietin (TSLP) and its downstream molecules in the development of ocular allergic inflammation using a short ragweed (SRW)-induced mouse model of allergic conjunctivitis (AC). BALB/c mice were topically challenged with SRW pollen after they were sensitized with SRW in the footpad. After the last SRW challenge, the corneal epithelium, conjunctiva, and cervical lymph nodes were harvested for total RNA extraction and gene expression by RT and real-time PCR, and whole eye globes were collected to make cryosections for immunohistochemical staining. Repeated topical challenges with SRW allergen generated typical signs of AC in mice. Compared with the untreated controls, TSLP mRNA expression and immunoreactivity were significantly increased in the corneal and conjunctival epithelia of SRW-induced AC mice. CD11c(+) and OX40L(+) immunoreactive cells largely infiltrated the conjunctiva with increased mRNA levels of CD11c, TSLPR, and OX40L detected in the corneal epithelium, conjunctiva, and cervical lymph nodes. CD4(+) Th2 cell infiltration was evidenced by increased levels of mRNA and immunoreactivity of CD4, IL-4, IL-5, and IL-13 in the ocular surface, mainly in the conjunctiva, accompanied by increased expression of OX40, STAT6, and GATA3, in AC mice. The maturation of immature DCs was observed with the use of TSLP containing conditioned media from corneal epithelial cultures exposed to polyI:C, which stimulates TSLP production. This study provides new findings regarding the role of local mucosal epithelial cells in the initiation of ocular allergic inflammation by producing a novel proallergic cytokine, TSLP, which activates dendritic cells to prime Th2 differentiation and allergic inflammation through the TSLP-TSLPR and OX40L-OX40 signaling pathway.

The regulatory role of thymic stromal lymphopoietin (TSLP) in maternal–fetal immune tolerance during early human pregnancy

Thymic stromal lymphopoietin (TSLP) is an IL-7-like cytokine, and the functional TSLP receptor (TSLPR) consists of a common IL-7 receptor alpha chain (IL-7Ralpha) and TSLP-specific gamma receptor chain (TSLPR-gamma). It has been demonstrated that TSLP plays an important role in the Th2 bias and regulatory T cell expansion of immune response and tolerance. A successful pregnancy, especially in the early phase, demonstrates features of a Th2 immune response and requires CD4(+)Foxp3(+) regulatory T cell expansion. We have found recently that TSLP-instructed decidual dendritic cells (dDCs) promote decidual CD4(+) T cells to produce Th2-type cytokines including IL-10, which is believed to be a key player in maternal-fetal tolerance. Phenotypic analyses have shown that the expanded cells are mainly CD4(+) Th2 cells and Foxp3(+) regulatory T cells. Our findings show that trophoblasts secrete TSLP that is able to instruct the dDCs to induce CD4(+) Th2 cell and Foxp3(+) regulatory T cell differentiation in decidual CD4(+) T cells.

Regulation of Helminth-Induced Th2 Responses by Thymic Stromal Lymphopoietin

Thymic stromal lymphopoietin was recently identified as a master switch for the development of allergen-driven Th2 responses. However, the role of thymic stromal lymphopoietin (TSLP) in the development of helminth-induced Th2 responses is unclear. Here, using TSLPR(-/-) mice, we show that while TSLPR signaling participates in the development of Schistosoma mansoni egg-induced CD4(+) Th2 responses, it plays only a transient role in the development of Th2-dependent pathology in the lung, liver, and intestine. Studies conducted in a pulmonary granuloma model showed that while a reduction in IL-4/IL-13-dependent granulomatous inflammation and tissue eosinophilia was observed in TSLPR(-/-) mice undergoing a primary response, lesion formation was not affected during a secondary granulomatous response, even though IL-5 and IL-13 were modestly reduced in the knockout mice. To evaluate the importance of TSLPR signaling in the development of a chronic Th2-dependent response, TSLPR(-/-) mice were also infected with S. mansoni cercariae. Here, the only significant difference noted in TSLPR(-/-) mice was a modest decrease in liver fibrosis in acutely infected animals. The transient decrease in fibrosis was associated with increased production of the antifibrotic cytokine IFN-gamma and decreased production of the profibrotic cytokine IL-13. Although the altered cytokine response persisted in chronically infected TSLPR(-/-) mice, it failed to reduce granuloma formation or fibrosis, confirming that TSLPR signaling plays a limited role in the development of chronic Th2-dependent pathology. Collectively, these findings suggest that while TSLPR signaling serves a key role in allergen-driven Th2 responses, it exerts minor regulatory activity during this chronic helminth infection.

RSV-induced expression of TSLP and asthma development (79.13)

Abstract Early infection with Respiratory Syncytial Virus (RSV) has long been recognized to predispose certain individuals towards the development of asthma. The immune response to RSV is unique in that it consists of protective Th1 and immunopathologic Th2-type features. Though much is known about the pathology of this disease it is still unclear how RSV infection leads to asthma development. Thymic Stromal Lymphopoietin (TSLP) is a cytokine that has been shown to be both necessary and sufficient for the development of asthma. Mice that express a lung-specific TSLP transgene (SPC-TSLP) develop a spontaneous and progressive asthma-like disease while TSLPRKO mice are highly resistant to disease in an antigen-specific asthma model. In this study we highlight a possible role for TSLP as the link between RSV infection and asthma development. We demonstrate that TSLP overexpression results in sensitization and the development of allergy to environmental antigens. Further, we show for the first time that RSV and its relative, Sendai Virus, lead to increases in TSLP expression by airway epithelial cells both in vitro and in vivo. Taken together these data suggest that TSLP induced by RSV during primary infection may increase susceptibility or directly result in asthma development. Additionally, in this study we show that the RIG-I viral recognition pathway represents a novel pathway leading to TSLP expression.

Overexpression of thymic stromal lymphopoietin in allergic rhinitis

Conclusion. Thymic stromal lymphopoietin (TSLP) played an important role in the pathogenesis of allergic rhinitis (AR) and can be regarded a potential therapeutic target for the management of AR. Objective. To evaluate the possible role of TSLP in the pathogenesis of AR. Patients and methods. We enrolled 16 patients of AR to investigate the expression of TSLP in nasal mucosa and evaluate the link of TSLP and interleukin-4 (IL-4). Expression of TSLP was detected by immunohistochemical analysis and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), and concentrations of TSLP and IL-4 were measured by enzyme-linked immunosorbent assay (ELISA). Results. TSLP was detected in all samples and the mRNA and protein expression of TSLP is increased significantly in AR nasal mucosa compared with normal control (P<0.05). TSLP production is tightly correlated with IL-4 and severity of AR (P<0.05).