Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Thymic Stromal Lymphopoietin (TSLP)

Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101973

Historical Background

Thymic stromal lymphopoietin (TSLP) was initially identified in conditioned medium from a murine thymic stromal cell line Z210R.1 as a cytokine that supports B cell development (Friend et al. 1994). It promotes the development of B220+/IgM+ immature B cells from cultured fetal liver cells and supports the long-term growth of a B cell line NAG8/7 in vitro. TSLP is a paralog of IL-7 and can substitute for IL-7 in the B cell development in vitro (Ray et al. 1996). In 2000, TSLP was found to signal through a heterodimeric receptor consisting of TSLP receptor (TSLPR) and IL-7 receptor alpha chain (IL-7Rα) (Pandey et al. 2000; Park et al. 2000). Human TSLP was cloned and characterized in 2001 although it shows only 43% amino acid sequence identity to murine TSLP (Quentmeier et al. 2001). In vivo studies with mouse model and in vitro studies showed that TSLP promotes Th2 differentiation and plays a pivotal role in the development and progression of allergic diseases.

TSLP Expression

TSLP gene contains multiple exons and is expressed in a wide variety of cell types including epithelial cells, epidermal keratinocytes, airway smooth muscle cells, fibroblasts, mast cells, dendritic cells, trophoblasts, cancer cells, and cancer-associated cells. In mouse, Tslp gene expresses two transcript variants. Only one variant is coding RNA, and a single form of TSLP protein has been described in mouse to date. However, human TSLP gene is transcribed into three transcript variants, one of which is noncoding RNA. The rest two transcripts derived from two different putative promoters are translated into two TSLP isoforms (Fornasa et al. 2015). When compared with the short isoform (sTSLP), the long isoform (lTSLP) contains 96 additional amino acids at the N-terminus. In addition to the difference in length, these two isoforms differ in their expression. The sTSLP is constitutively expressed in healthy tissues including salivary glands, gut, skin, and oral epithelium (Fornasa et al. 2015; Bjerkan et al. 2015). The expression of TSLP isoforms in intestinal epithelial cells and skin keratinocytes is differentially regulated under the condition of ulcerative colitis and atopic dermatitis, or when exposed to inflammatory stimuli (Fornasa et al. 2015). Before the discovery of the short isoform, the studies on the expression of human TSLP were mostly for the long isoform.

Transcription of TSLP is controlled by NF-κB pathway and transcription factor activator protein 1 (AP-1). NF-κB and AP-1 binding sites were identified at the promoter of TSLP gene (Lee and Ziegler 2007; Cultrone et al. 2013). Activation of NF-κB pathway and recruit of AP1 to TSLP promoter is required for TSLP expression. TSLP is also regulated by other transcription factors such as IFN regulatory factor 3 (IRF3) in intestines. In cooperation with NF-κB, IRF3 dramatically activates TSLP expression by binding to a response element, which is about 200 bp upstream to transcription start site of murine Tslp gene (Negishi et al. 2012).

TSLP is mainly expressed by cells that are at the barrier interfaces between environment and body, such as epithelial cells of gut and airway and skin keratinocytes. Therefore, TSLP expression is upregulated by a wide range of environmental stimuli including allergen sources, viruses, microbes, helminths, diesel exhaust, cigarette smoke, and chemicals. Endogenous factors that regulate TSLP expression and production include cytokine milieu, immunoglobulins, lipid mediators, and abnormal activity of proteases. Proinflammatory TNF-α and Th2 cytokines synergistically induce the production of TSLP in human skin keratinocytes, human colonic epithelial cells, and nasal polyp fibroblasts (Bogiatzi et al. 2007; Tanaka et al. 2010; Nonaka et al. 2010). IL-4 or IL-13 alone is able to significantly upregulate TSLP transcription in human airway epithelial cells (Kato et al. 2007). Although IL-4 alone does not affect the TSLP transcription in human bronchial mast cells, preincubation of the cells with IL-4 significantly enhanced the FcεRI-mediated TSLP mRNA expression and intracellular production (Okayama et al. 2009). Other IgE-mediated TSLP upregulation is observed in human airway smooth muscle (Redhu et al. 2011). Lysophosphatidic acid is a bioactive phospholipid and is elevated in bronchoalveolar lavage fluid from asthmatic lung. Studies showed that lysophosphatidic acid induces release of TSLP from human bronchial epithelial cells (Medoff et al. 2009). Abnormal activity of proteases can induce TSLP expression such as in skin of patients with Netherton syndrome. Netherton syndrome is associated with mutations in the serine protease inhibitor Kazal-type 5 (SPINK5) gene which encodes the protease inhibitor lymphoepithelial Kazal-type–related inhibitor (LEKTI). The impaired function of LEKTI leads to excessive activity of endogenous serine proteases like kallikrein 5, which, in turn, cleaves and activates proteinase-activated receptor 2 on keratinocytes. Activated proteinase-activated receptor 2 then induces overexpression of TSLP through NF-kB signaling (Briot et al. 2009).

In addition, some medicines used for asthma and COPD treatment can induce TSLP expression. For example, β2-adrenergic receptor agonists are a class of drugs used as bronchodilators in the treatment of asthma and COPD. Adverse effects of β2-adrenergic receptor agonists on asthma control have recently been discovered. β2-adrenergic receptor agonists significantly enhance the cytokine-induced TSLP production by primary human lung tissue cells, and the increase in TSLP is mediated by upregulated intracellular cAMP (Futamura et al. 2010).

TSLP Signaling Pathway

TSLP signals through a heterodimeric receptor complex composed of TSLP receptor (TSLPR) subunit, encoded by cytokine receptor-like factor 2 (CRLF2) gene and the alpha chain of IL-7 receptor (IL-7Rα/CD127). Sequence alignment of IL-7Rα cytoplasmic domains among eight species including human and mouse showed two conserved tyrosine residues (Y449 and Y456 in human IL-7Rα) in the C-terminal region. The intracellular region of TSLPR proteins has only one conserved tyrosine residue (Y368 in human TSLPR) in the C-terminus. Site-directed mutagenesis revealed that cytoplasmic tyrosine residues in IL-7Rα and TSLPR play a redundant role in TSLP signal transduction, and TSLP requires at least one cytoplasmic tyrosine residue of the TSLP receptor complex to transmit proliferative signals (Zhong and Pandey 2010).

Many types of immune cells such as dendritic cells, B cells, mast cells, regulatory T (Treg) cells, conventional CD4+ T cells, and CD8+ T cells are cellular target for TSLP. In addition, TSLP also effects on nonimmune cells such as keratinocytes, trophoblast cells, and some cancer cells. These cells express TSLP receptor complex either constitutively or after being activated.

Upon binding to the receptor, TSLP stimulates multiple signal transduction pathways. Studies have shown that TSLP stimulation on primary CD4+ T cells activates JAK/STAT pathway by phosphorylating JAK1 and JAK2 and thereby induces the phosphorylation of STAT5 proteins (Isaksen et al. 1999; Rochman et al. 2010). In human myeloid DCs (mDCs), TSLP induces phosphorylation and activation of all known STATs except for STAT2 through robust and prolonged activation of JAK1 and JAK2 (Arima et al. 2010).

TSLP can also activate the mitogen-activated protein kinases (MAPKs) (ERK1/2, p38, and JNK) pathways in human airway smooth muscle cells to induce chemokines/cytokine expression (Shan et al. 2010). In human myeloid dendritic cells, TSLP activates phosphoinositide 3-kinase (PI3K)–Akt pathway in addition to the mitogen-activated protein kinases (MAPKs) pathways (Arima et al. 2010). In addition, TSLP can activate TSLPR-dependent PI3K/Akt signaling pathway inside platelet and thereby induce platelet aggregation (Dong et al. 2015).

Functions in Immune System

In Dendritic Cells

Monocytes and dendritic cell populations are known to have the highest coexpressions of human TSLPR and IL-7Rα. TSLP has the capacity to potently enhance the maturation and function of CD11c+ human myeloid DCs, as evidenced by the strong induction of the MHC II, costimulatory molecules CD40 and CD80, and release of Th2 cell-attracting chemokines (Soumelis et al. 2002). Similarly, murine bone marrow–derives DCs responded to TSLP treatment by producing chemokine CCL17 and increasing MHC II and costimulatory protein expression (Zhou et al. 2005).

TSLP produced by epithelial cells or keratinocytes can skew the developing immune response toward a proallergic state through its direct action on DCs. This concept is supported by studies showing that TSLP directly activates DCs to express OX40L to prime naive CD4+ T cells to differentiate into proinflammatory Th2 cells characterized by high amounts of IL-4, −5, −13, and TNF-α but not IL-10 and IFN-γ (Ito et al. 2005; Soumelis et al. 2002). In vivo studies also demonstrated TSLP induced Th2 inflammation was mediated by OX40-OX40L interaction. Treating mice with OX40L-blocking antibodies substantially inhibited TSLP-induced immune responses in the lung and skin, and also inhibited antigen-driven Th2 inflammation in mouse and nonhuman primate models of asthma, including Th2 inflammatory cell infiltration and cytokine secretion (Seshasayee et al. 2007). OX40L expressed by TSLP treated DCs was also required for prolonged DC-T cognate formation and contributed to drive the homeostatic proliferation of Th2 memory cells (Wang et al. 2006).

In CD4+ T Cells

TSLP can induce Th2 cell differentiation directly or indirectly through antigen presenting cells. TSLP induces immediate IL-4 production by CD4 T cells and thus drives Th2 differentiation in the absence of exogenous IL-4 and APCs (Omori and Ziegler 2007). TSLP induces expression of the antiapoptotic factor Bcl-2 in Th2 cells and enhances their proliferation and survival (Kitajima et al. 2011; Wang et al. 2015). TSLP signaling in CD4+ T cells is also required for the recall response of the memory cells to local antigen challenge (Wang et al. 2015).

A newly identified Th9 helper subset specializing in IL-9 secretion plays an important role in human atopic diseases. Although lower than in Th2 cells, TSLPR expression in Th9 cells is higher than in Th1 and Th17 cells. In vitro and in vivo studies demonstrate that TSLP promotes Th9 cell differentiation and function either directly (Yao et al. 2013) or indirectly through activation of mDC (Froidure et al. 2014). Lung-specific expression of TSLP in transgenic mice stimulates IL-9 production in vivo and treatment with IL-9 neutralizing antibody attenuates TSLP-induced airway inflammation (Yao et al. 2013).

In Regulatory T Cells

Several studies have shown that TSLP promotes thymic Tregs development. In humans, TSLP is constitutively expressed in Hassall’s corpuscles of thymus where it promotes the differentiation of CD4+CD25+FOXP3+ thymic regulatory T cells by activating CD11c+ myeloid dendritic cells and plasmacytoid dendritic cells (Watanabe et al. 2005; Hanabuchi et al. 2010). In mouse, TSLP can directly induce Foxp3 expression in purified CD4 single positive thymocytes (Jiang et al. 2006; Lee et al. 2008). Despite these effects, it is unlikely that TSLP is absolutely required for Treg development. Animals deficient for TSLPR had relatively normal Treg development (Mazzucchelli et al. 2008). However, mice deficient for IL-7Rα or IL-7 and TSLPR double mutant showed greatly reduced Treg development in thymus but no effects on survival of mature peripheral Tregs, suggesting IL-7 and TSLP acting redundantly in thymic Treg development (Mazzucchelli et al. 2008).

In periphery, TSLP exerts both positive and negative effect on Treg induction. TSLP is able to induce Tregs from mouse naïve CD4 T-cells indirectly by stimulating bone marrow dendritic cells (Besin et al. 2008). In addition, human intestinal epithelial cell-derived TSLP is required for the generation of tolerogenic DCs that are capable of converting naïve CD4 T cells into Tregs (Iliev et al. 2009). However, TSLP directly inhibits the induction of iTregs from human and mouse naïve CD4 T cells in vitro (Lei et al. 2011). Consistent with the suppressive effect over Treg induction, children with asthma have elevated serum level of TSLP which is negatively correlated with Treg cells (Chauhan et al. 2015).

Human TSLP also directly modulate Treg functions. Pulmonary Tregs from patients with allergic asthma exhibited a significant decrease in suppressive activity and IL-10 production. Elevated pulmonary TSLP directly impaired Treg function as allergic asthmatic bronchoalveolar lavage fluid could suppress IL-10 production and regulatory function of pulmonary Tregs isolated from healthy controls in a TSLP-dependent manner (Nguyen et al. 2010).

In CD8+ T Cells

TSLP can increase the proliferation and activity of CD8 T cells. TSLP activates both STAT5 and Akt and induces Bcl-2 in CD8 cells, and increases CD8 T cell survival both in vitro and in vivo (Rochman and Leonard 2008). Influenza infection induces TSLP production by lung epithelial cells in the respiratory tract. The induced TSLP acts directly on CD8 T cells and helps mount the antiviral immune response by increasing CD8 T-cell proliferation (Shane and Klonowski 2014). The Influenza-induced TSLP can also enhance the function of virus-specific CD8 T cells in the lung indirectly by activating the maturation of newly recruited CD11b+ dendritic cells (Yadava et al. 2013).

In B Cells

TSLP was initially identified as a cytokine that promotes B cell development in vitro. In vivo studies with transgenic mice showed that TSLP overexpressed in skin increases bone marrow B cell lymphopoiesis at an early stage of B cell development. TSLP takes effect on late pro-B cell subset and upregulates cell cycle factors such as c-Myc and cyclin D2. As a consequence, exogenous TSLP expands the late pro-B cell population and induces premature migration of immature cells to the periphery (Astrakhan et al. 2007). Similarly, a large amount of TSLP released into systemic circulation by Notch-deficient keratinocytes during neonatal hematopoiesis induces drastic expansion of peripheral pre- and immature B-lymphocytes, which causes B-lymphoproliferative disorder and further death (Demehri et al. 2008). However, TSLPR-deficiency in mice does not cause defect in B cell development in vivo. When compared with wild-type mice, the TSLPR-KO mice generate similar ratios of bone marrow pro-B cells, pre-B cells, or mature B cells in the bone marrow B-lymphocyte populations. The frequency of B cells in spleen is also normal in KO mice. Therefore, TSLP signaling pathway is not essential to murine B cell development (Carpino et al. 2004).

In humans, IL-7α chain and TSLPR are expressed at early stages of B cell development and TSLP promotes B cells differentiation by inducing the proliferation of B cell progenitors. The transcripts of both subunits of TSLP receptor complex are expressed in hematopoietic stem cells (LinCD34+CD38) from fetal liver, multilineage-committed progenitor cells (MLCP) (LinCD34+CD38+CD19), and pro-B cells (LinCD34+CD38+CD19+) from both fetal liver and fetal bone marrow (BM). TSLP stimulation induces tyrosine phosphorylation of STAT5 only in a fraction of fetal BM- and fetal liver-derived MLCP and pro-B cells among the cells tested, which indicates these two subsets of cells express functional TSLP receptor complex. Consistent with the TSLP receptor expression, TSLP induces the proliferation of MLCP, pro-B cells, and pre-B cells derived from fetal liver, and MLCP and pro-B cells from fetal BM in vitro (Scheeren et al. 2010).

Pathophysiological Functions

In Allergic Diseases


TSLP can induce differentiation and proliferation of Th2 cells and activate dendritic cells to produce Th2 cell–attracting chemokines CCL17 and CCL22 (Soumelis et al. 2002; Zhou et al. 2005). TSLPR deficiency considerably attenuates the OVA-induced lung allergic inflammation with decreased frequency of eosinophils in the BAL fluid, decreased leukocyte infiltration, and less mucus production (Zhou et al. 2005; Al-Shami et al. 2005). In contrast, mice overexpressing TSLP specifically in lung epithelial cells develop an eosinophilic airway inflammatory disease with asthma-like characteristics. These mice show Th2-biased CD4+ T cell infiltration, eosinophilia, increased serum IgE, airway hyper-responsiveness, and airway remodeling (Zhou et al. 2005). Th2 responses play an essential role in TSLP-induced asthma-like diseases since (1) TSLP-induced airway hyperresponsiveness, airway inflammation, eosinophilia, and goblet cell metaplasia are greatly reduced in IL-4 deficiency background; (2) Stat6 deficiency eliminates these asthma-like symptoms; (3) therapeutic blockade of both IL-4 and IL-13 signaling reverses asthma-like symptoms (Zhou et al. 2008).

In humans, airway expression of TSLP is increased in patients with severe asthma (Nguyen et al. 2010). The level of TSLP correlates with Th2-attracting chemokines and disease severity, and the number of cells expressing TSLP and Th2-attracting chemokines is significantly increased in severe asthma (Ying et al. 2005; Ying et al. 2008). In a cynomolgus monkey model of asthma, blockade of TSLPR with anti-TSLPR mAb reduces allergic inflammation. The antibody treatment reduces airway resistance in response to allergen challenge, eosinophil counts, and IL-13 level in bronchoalveolar lavage (BAL) fluid (Cheng et al. 2013).

Atopic Dermatitis

In humans, the expression of TSLP highly correlates with the disease. High level of TSLP is expressed by keratinocytes in lesional skin but not in nonlesional skin of patients with atopic dermatitis or skin lesions from patients with nickel-induced allergy contact dermatitis or cutaneous lupus erythematosus (Soumelis et al. 2002). In mice, overexpressed TSLP in skin induces atopic dermatitis-like phenotype. The mice show dermal infiltration of lymphocytes, mast cells, and eosinophils. Th2 cytokines are increased in effected skin. In addition, serum IgE level is elevated (Yoo et al. 2005). Likewise, aberrant skin TSLP expression in mice with keratinocyte-selective ablation of retinoid X receptors (RXRα and RXRβ) (Li et al. 2005) or keratinocyte-specific deletion of total Notch signaling (Dumortier et al. 2010; Demehri et al. 2008) developed a chronic dermatitis syndrome similar to that observed in AD patients. Consistent with a requirement for TSLP in allergic skin inflammation, epicutaneously sensitized and challenged TSLPR-deficient mice showed greatly reduced allergic skin inflammation compared with WT mice, with decreased number of eosinophils and decreased local expression of Th2 cytokines in the skin (He et al. 2008).

One of the main symptoms of atopic dermatitis is itch. Itch-induced scratching disrupts skin barrier and exposes epidermal cells to allergens and microbes, which aggravates the inflammation symptoms. Keratinocyte-derived TSLP has been shown to act directly on a subset of TRPA1-positive sensory neurons to trigger robust itch behaviors (Wilson et al. 2013). The discovery of TSLP as a pruritogen suggests that TSLP might be able to maintain/promote atopic dermatitis through provoking the itch-scratching behavior (Turner and Zhou 2014).

Allergic Rhinitis

Allergic asthma, atopic dermatitis, and allergic rhinitis are referred to as the atopic triad. Like allergic asthma and atopic dermatitis, allergic rhinitis is also characterized by Th2-type allergic inflammation. Clinical studies show a tight correlation of the TSLP expression to allergic rhinitis. TSLP mRNA and protein are upregulated significantly in nasal mucosa and nasal epithelial cells of allergic rhinitis patients when compared with normal control. TSLP production is highly correlated to IL-4 expression, nasal eosinophil counts, and severity of the disease (Matsuda et al. 2010; Miyata et al. 2008). In mouse model of allergic rhinitis, the development of the disease is inhibited with TSLP neutralizing antibody administrated during the challenge phase of OVA (Miyata et al. 2008).

In Other Immune-Mediated Diseases

Many studies have shown that dysregulated TSLP also induces other immune diseases such as rheumatoid arthritis, COPD, inflammatory bowel diseases, EOE, psoriasis, and systemic sclerosis.

The level of TSLP is increased in synovial fluid specimens from patients with rheumatoid arthritis when compared with those from patients with osteoarthritis. TSLP is produced by synovial fibroblasts of rheumatoid arthritis and is upregulated by TNF-alpha. Furthermore, in mouse models of arthritis, administration of TSLP exacerbates the severity of collagen-induced arthritis but TSLP neutralization ameliorates arthritis induced by anti-type II collagen antibody (Hartgring et al. 2011; Koyama et al. 2007). In addition, TSLPR deficiency reduces the severity of chronic relapsing proteoglycan-induced arthritis (Hartgring et al. 2011). Combined with other findings, these results indicate the role of TSLP pathway in rheumatoid arthritis.

Dysregulation of TSLP expression has been shown to cause inflammatory bowel diseases. Lack of TSLP expression by intestinal epithelial cells is involved in Crohn’s disease. However, overexpressed TSLP by intestinal epithelial cells is believed to result in Th2-associated ulcerative colitis (Park et al. 2017).

In Cancer

Evasion of immune attack is a hallmark of tumor initiation and progress. TSLP has been reported to either foster or inhibit cancer development. The effect of TSLP on tumor growth depends on tumor type and stage. TSLP can be produced by human breast tumor cells and pancreatic cancer-associated fibroblast cells. The TSLP subsequently induces Th2-mediated inflammation in tumor microenvironment, which promotes tumor development (De Monte et al. 2011; Pedroza-Gonzalez et al. 2011). TSLP is also produced by gastric cancer cells, and significant correlation has been observed between TSLP overexpression and gastric cancer metastasis to lymph nodes (Barooei et al. 2015). In mice, knockdown of TSLP expression in 4 T1 cancer cells alone was sufficient to almost completely abrogate cancer progression and lung metastasis. Tumor growth and metastasis were significantly suppressed when 4 T1 adenocarcinoma and B16 melanoma were implanted into TSLPR-deficient mice (Olkhanud et al. 2011).

Leukemic lymphoblasts from some patients with B cell precursor acute lymphoblastic leukemia express TSLPR. TSLP stimulation enhances the proliferation of leukemic lymphoblast cells that express the highest level of TSLPR (Vetter et al. 2016). Furthermore, TSLP has been found to induce the growth of cutaneous T-cell lymphoma by directly stimulating tumor cells and inducing Th2-dominant tumor environment (Takahashi et al. 2016).

Surprisingly, TSLP can mount antitumor immune response to some types of tumor. TSLP-induced inflammation has been shown to prevent cutaneous carcinogenesis in mice, in which suppression of canonical Wnt pathway and elimination of Notch-deficient epidermal cells are involved (Di Piazza et al. 2012; Demehri et al. 2012). TSLP employs a different mechanism to inhibit human colon tumor growth. In patients with colon cancer, TSLP levels negatively correlate with the clinical score. Colon cancer cells express TSLPR and TSLP promotes apoptosis of colon cancer cells (Yue et al. 2016). Antitumor response against some cancers by TSLP is tumor stage-specific. Although TSLP promotes progress of breast cancer, it blocks breast carcinogenesis at an early adenoma-like stage. Similar inhibitory effect of TSLP has been observed on pancreatic cancer (Demehri et al. 2016).


Dysregulated TSLP induces allergic diseases by multiple mechanisms such as activating DCs and mast cells, promoting the differentiation of Th2 and Th9 subsets, and inhibiting Tregs. Therefore, targeting TSLP, suppressing the expression and production of TSLP, or blocking TSLP signaling pathway may inhibit multiple biologic pathways involved in allergic diseases and thus serves as novel therapies for these diseases. Indeed, a recent published double-blind, placebo-controlled clinical study demonstrated that patients treated with a human TSLP antibody significantly reduced allergen-induced FEV1 decrease, blood and sputum eosinophil counts, and the fraction of exhaled nitric oxide compared to placebo controls (Gauvreau et al. 2014).

Infants with AD have an increased risk of developing asthma and rhinitis at later ages. This progression of atopic manifestations from AD to asthma to allergic rhinitis is known as the “atopic march.” Due to its ability to promote Th2 immune responses, TSLP has been implicated as an underlying factor to drive the “atopic march.” Some suggested that AD skin-derived TSLP promoted epicutaneous sensitization against allergens and the same allergen now can elicit allergic airway responses (Han et al. 2012; Leyva-Castillo et al. 2013). However, there is >1 year time lag for infants with AD to become sensitized against aerosol allergens (Rhodes et al. 2002). Thus, it is unlikely that TSLP drives the “atopic march” through promoting epicutaneous sensitization. Others propose that skin-derived TSLP enhances airway Th2 inflammation (Demehri et al. 2009; Zhang et al. 2009). However, the use of Alum as an adjuvant to sensitize the mice and the presence of high concentrations of serum TSLP make it questionable whether such scenario is physiological. Although a positive link between TSLP and atopic march would suggest new strategies to prevent asthma development in high-risk infant with severe AD, more studies are needed to establish such a link and mechanisms underlie the link.

Inflammation can affect every aspect of tumor development and progression as well as the responses to therapies. Studies demonstrating that progression of breast cancer (Olkhanud et al. 2011; Pedroza-Gonzalez et al. 2011) and pancreatic cancer (De Monte et al. 2011) are associated with TSLP-dependent induction of Th2-type inflammation will surely stimulate interest among oncology researchers. Targeting TSLP could be an attractive new therapeutic treatment against various cancers.


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© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of PediatricsWells Center for Pediatric ResearchIndianapolisUSA
  2. 2.Department of Microbiology and ImmunologyIndiana University School of MedicineIndianapolisUSA