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TSLP: from allergy to cancer

Nature Immunology volume 20, pages 1603–1609 (2019)Cite this article

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Abstract

The cytokine TSLP has been shown to be a key factor in maintaining immune homeostasis and regulating inflammatory responses at mucosal barriers. While the role of TSLP in type 2 immune responses has been investigated extensively, recent studies have found an expanding role for TSLP in inflammatory diseases and cancer. In this Review, we will highlight major recent advances in TSLP biology, along with results from emerging clinical trials of anti-TSLP agents used for the treatment of a variety of inflammatory conditions.

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Fig. 1: Functions of TSLP in promoting type 2 responses.
Fig. 2: Role of the IL-1α–TSLP axis in breast cancer.

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References

  1. Sims, J. E. et al. Molecular cloning and biological characterization of a novel murine lymphoid growth factor. J. Exp. Med. 192, 671–680 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Levin, S. D. et al. Thymic stromal lymphopoietin: a cytokine that promotes the development of IgM+ B cells in vitro and signals via a novel mechanism. J. Immunol. 162, 677–683 (1999).

    CAS  PubMed  Google Scholar 

  3. Friend, S. L. et al. A thymic stromal cell line supports in vitro development of surface IgM+ B cells and produces a novel growth factor affecting B and T lineage cells. Exp. Hematol. 22, 321–328 (1994).

    CAS  PubMed  Google Scholar 

  4. Ray, R. J., Furlonger, C., Williams, D. E. & Paige, C. J. Characterization of thymic stromal-derived lymphopoietin (TSLP) in murine B cell development in vitro. Eur. J. Immunol. 26, 10–16 (1996).

    CAS  PubMed  Google Scholar 

  5. Reche, P. A. et al. Human thymic stromal lymphopoietin preferentially stimulates myeloid cells. J. Immunol. 167, 336–343 (2001).

    CAS  PubMed  Google Scholar 

  6. Quentmeier, H. et al. Cloning of human thymic stromal lymphopoietin (TSLP) and signaling mechanisms leading to proliferation. Leukemia 15, 1286–1292 (2001).

    CAS  PubMed  Google Scholar 

  7. Park, L. S. et al. Cloning of the murine thymic stromal lymphopoietin (TSLP) receptor: formation of a functional heteromeric complex requires interleukin 7 receptor. J. Exp. Med. 192, 659–670 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Pandey, A. et al. Cloning of a receptor subunit required for signaling by thymic stromal lymphopoietin. Nat. Immunol. 1, 59–64 (2000).

    CAS  PubMed  Google Scholar 

  9. Fujio, K. et al. Molecular cloning of a novel type 1 cytokine receptor similar to the common gamma chain. Blood 95, 2204–2210 (2000).

    CAS  PubMed  Google Scholar 

  10. Tonozuka, Y. et al. Molecular cloning of a human novel type I cytokine receptor related to δ1/TSLPR. Cytogenet. Cell Genet. 93, 23–25 (2001).

    CAS  PubMed  Google Scholar 

  11. Barnes, P. J. Targeting cytokines to treat asthma and chronic obstructive pulmonary disease. Nat. Rev. Immunol. 18, 454–466 (2018).

    CAS  PubMed  Google Scholar 

  12. Roan, F., Obata-Ninomiya, K. & Ziegler, S. F. Epithelial cell-derived cytokines: more than just signaling the alarm. J. Clin. Invest. 129, 1441–1451 (2019).

    PubMed  Google Scholar 

  13. Zhang, Y. & Jin, L. P. Effects of TSLP on obstetrical and gynecological diseases. Am. J. Reprod. Immunol. 77, e12612 (2017).

    Google Scholar 

  14. Park, J. H., Jeong, D. Y., Peyrin-Biroulet, L., Eisenhut, M. & Shin, J. I. Insight into the role of TSLP in inflammatory bowel diseases. Autoimmun. Rev. 16, 55–63 (2017).

    CAS  PubMed  Google Scholar 

  15. Harada, M. et al. Functional analysis of the thymic stromal lymphopoietin variants in human bronchial epithelial cells. Am. J. Respir. Cell Mol. Biol. 40, 368–374 (2009).

    CAS  PubMed  Google Scholar 

  16. Varricchi, G. et al. Thymic Stromal lymphopoietin isoforms, inflammatory disorders, and cancer. Front. Immunol. 9, 1595 (2018).

    PubMed  PubMed Central  Google Scholar 

  17. Xie, Y., Takai, T., Chen, X., Okumura, K. & Ogawa, H. Long TSLP transcript expression and release of TSLP induced by TLR ligands and cytokines in human keratinocytes. J. Dermatol. Sci. 66, 233–237 (2012).

    CAS  PubMed  Google Scholar 

  18. Datta, A. et al. Evidence for a functional thymic stromal lymphopoietin signaling axis in fibrotic lung disease. J. Immunol. 191, 4867–4879 (2013).

    CAS  PubMed  Google Scholar 

  19. Martin Mena, A. et al. The expression of the short isoform of thymic stromal lymphopoietin in the colon is regulated by the nuclear receptor peroxisome proliferator activated receptor-γ and is impaired during ulcerative colitis. Front. Immunol. 8, 1052 (2017).

    PubMed  PubMed Central  Google Scholar 

  20. Fornasa, G. et al. Dichotomy of short and long thymic stromal lymphopoietin isoforms in inflammatory disorders of the bowel and skin. J. Allergy Clin. Immunol. 136, 413–422 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Bjerkan, L. et al. The short form ofTSLP is constitutively translated in human keratinocytes and has characteristics of an antimicrobial peptide. Mucosal Immunol. 8, (49–56 (2015).

    Google Scholar 

  22. Sonesson, A. et al. Thymic stromal lymphopoietin exerts antimicrobial activities. Exp. Dermatol. 20, 1004–1010 (2011).

    CAS  PubMed  Google Scholar 

  23. Dong, H. et al. Distinct roles of short and long thymic stromal lymphopoietin isoforms in house dust mite-induced asthmatic airway epithelial barrier disruption. Sci. Rep. 6, 39559 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Hammad, H. & Lambrecht, B. N. Barrier epithelial cells and the control of type 2 immunity. Immunity 43, 29–40 (2015).

    CAS  PubMed  Google Scholar 

  25. Ito, T. et al. TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand. J. Exp. Med. 202, 1213–1223 (2005). Ref. 25 showed that TSLP signaling by DCs leads to expression of OX40L, which promotes T H 2 differentiation.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Löhning, M. et al. T1/ST2 is preferentially expressed on murine Th2 cells, independent of interleukin 4, interleukin 5, and interleukin 10, and important for Th2 effector function. Proc. Natl Acad. Sci. USA 95, 6930–6935 (1998).

    PubMed  Google Scholar 

  27. Ochiai, S. et al. Thymic stromal lymphopoietin drives the development of IL-13+ Th2 cells. Proc. Natl Acad. Sci. USA 115, 1033–1038 (2018).

    CAS  PubMed  Google Scholar 

  28. Omori, M. & Ziegler, S. Induction of IL-4 expression in CD4+ T cells by thymic stromal lymphopoietin. J. Immunol. 178, 1396–1404 (2007).

    CAS  PubMed  Google Scholar 

  29. Kitajima, M., Lee, H. C., Nakayama, T. & Ziegler, S. F. TSLP enhances the function of helper type 2 cells. Eur. J. Immunol. 41, 1862–1871 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Astrakhan, A. et al. Local increase in thymic stromal lymphopoietin induces systemic alterations in B cell development. Nat. Immunol. 8, 522–531 (2007).

    CAS  PubMed  Google Scholar 

  31. Kim, B. S. et al. TSLP elicits IL-33-independent innate lymphoid cell responses to promote skin inflammation. Sci. Transl. Med 5, 170ra (2013).

    Google Scholar 

  32. Han, H. et al. Thymic stromal lymphopoietin amplifies the differentiation of alternatively activated macrophages. J. Immunol. 190, 904–912 (2013).

    CAS  PubMed  Google Scholar 

  33. Siracusa, M. C. et al. TSLP promotes interleukin-3-independent basophil haematopoiesis and type 2 inflammation. Nature 477, 229–233 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Salabert-Le Guen, N. et al. Thymic stromal lymphopoietin does not activate human basophils. J. Allergy Clin. Immunol. 141, 1476–1479.e1476 (2018).

    PubMed  Google Scholar 

  35. Leyva-Castillo, J. M. et al. Skin thymic stromal lymphopoietin initiates Th2 responses through an orchestrated immune cascade. Nat. Commun. 4, 2847–2847 (2013).

    PubMed  Google Scholar 

  36. Chang, J., Mitra, N., Hoffstad, O. & Margolis, D. J. Association of filaggrin loss of function and thymic stromal lymphopoietin variation with treatment use in pediatric atopic dermatitis. JAMA Dermatol. 153, 275–281 (2017).

    PubMed  Google Scholar 

  37. Soumelis, V. et al. Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP. Nat. Immunol. 3, 673–680 (2002). Ref. 37 was the first report of a role for TSLP in allergic disease.

    CAS  PubMed  Google Scholar 

  38. Sano, Y. et al. Thymic stromal lymphopoietin expression is increased in the horny layer of patients with atopic dermatitis. Clin. Exp. Immunol. 171, 330–337 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Oyoshi, M. K., Larson, R. P., Ziegler, S. F. & Geha, R. S. Mechanical injury polarizes skin dendritic cells to elicit a TH2 response by inducing cutaneous thymic stromal lymphopoietin expression. J. Allergy Clin. Immunol. 126, 976–984 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Dumortier, A. et al. Atopic dermatitis-like disease and associated lethal myeloproliferative disorder arise from loss of Notch signaling in the murine skin. PLoS One 5, e9258 (2010).

    PubMed  PubMed Central  Google Scholar 

  41. Demehri, S. et al. Notch-deficient skin induces a lethal systemic B-lymphoproliferative disorder by secreting TSLP, a sentinel for epidermal integrity. PLoS Biol. 6, e123 (2008).

    PubMed  PubMed Central  Google Scholar 

  42. Han, H. et al. IL-33 promotes gastrointestinal allergy in a TSLP-independent manner. Mucosal Immunol. 11, 578 (2018).

    CAS  PubMed  Google Scholar 

  43. McCoy, E. S., Taylor-Blake, B. & Zylka, M. J. CGRPα-expressing sensory neurons respond to stimuli that evoke sensations of pain and itch. PLoS One 7, e36355 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Mack, M. R. & Kim, B. S. The itch-scratch cycle: a neuroimmune perspective. Trends Immunol. 39, 980–991 (2018).

    CAS  PubMed  Google Scholar 

  45. Wilson, S. R. et al. The epithelial cell-derived atopic dermatitis cytokine TSLP activates neurons to induce itch. Cell 155, 285–295 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Simpson, E. L. et al. Tezepelumab, an anti-thymic stromal lymphopoietin monoclonal antibody, in the treatment of moderate to severe atopic dermatitis: a randomized phase 2a clinical trial. J. Am. Acad. Dermatol. 80, 1013–1021 (2019).

    CAS  PubMed  Google Scholar 

  47. Guttman-Yassky, E. et al. GBR 830, an anti-OX40, improves skin gene signatures and clinical scores in patients with atopic dermatitis. J. Allergy Clin. Immunol. 144, 482–493.e7 (2019).

    CAS  PubMed  Google Scholar 

  48. Tsakok, T. et al. Does atopic dermatitis cause food allergy? A systematic review. J. Allergy Clin. Immunol. 137, 1071–1078 (2016).

    PubMed  Google Scholar 

  49. Lack, G., Fox, D., Northstone, K. & Golding, J. Factors associated with the development of peanut allergy in childhood. N. Engl. J. Med. 348, 977–985 (2003).

    PubMed  Google Scholar 

  50. Watson, C. T. et al. Integrative transcriptomic analysis reveals key drivers of acute peanut allergic reactions. Nat. Commun. 8, 1943 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Sherrill, J. D. et al. Variants of thymic stromal lymphopoietin and its receptor associate with eosinophilic esophagitis. J. Allergy Clin. Immunol. 126, 160–165.e3 (2010). Ref. 51 provided the first evidence that genetic variants of the TSLP pathway are involved in disease development.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Bartnikas, L. M. et al. Epicutaneous sensitization results in IgE-dependent intestinal mast cell expansion and food-induced anaphylaxis. J. Allergy Clin. Immunol. 131, 451–460.e6 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Noti, M. et al. Thymic stromal lymphopoietin-elicited basophil responses promote eosinophilic esophagitis. Nat. Med. 19, 1005–1013 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Torgerson, D. G. et al. Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations. Nat. Genet. 43, 887–892 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Hirota, T. et al. Genome-wide association study identifies three new susceptibility loci for adult asthma in the Japanese population. Nat. Genet. 43, 893–896 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Shikotra, A. et al. Increased expression of immunoreactive thymic stromal lymphopoietin in patients with severe asthma. J. Allergy Clin. Immunol. 129, 104–111 (2011).

    PubMed  Google Scholar 

  57. Wang, W. et al. Bronchial allergen challenge of patients with atopic asthma triggers an alarmin (IL-33, TSLP, and IL-25) response in the airways epithelium and submucosa. J. Immunol. 201, 2221–2231 (2018).

    CAS  PubMed  Google Scholar 

  58. Demehri, S., Morimoto, M., Holtzman, M. J. & Kopan, R. Skin-derived TSLP triggers progression from epidermal-barrier defects to asthma. PLoS Biol. 7, e1000067 (2009).

    PubMed  PubMed Central  Google Scholar 

  59. Zhang, Z. et al. Thymic stromal lymphopoietin overproduced by keratinocytes in mouse skin aggravates experimental asthma. Proc. Natl Acad. Sci. USA 106, 1536–1541 (2009).

    CAS  PubMed  Google Scholar 

  60. Han, J. et al. Responsiveness to respiratory syncytial virus in neonates is mediated through thymic stromal lymphopoietin and OX40 ligand. J. Allergy Clin. Immunol. 130, 1175–1186.e9 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Stier, M. T. et al. Respiratory syncytial virus infection activates IL-13-producing group 2 innate lymphoid cells through thymic stromal lymphopoietin. J. Allergy Clin. Immunol. 138, 814–824.e811 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Camelo, A. et al. IL-33, IL-25, and TSLP induce a distinct phenotypic and activation profile in human type 2 innate lymphoid cells. Blood Adv. 1, 577–589 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Kabata, H. et al. Thymic stromal lymphopoietin induces corticosteroid resistance in natural helper cells during airway inflammation. Nat. Commun. 4, 2675–2675 (2013).

    PubMed  Google Scholar 

  64. Liu, S. et al. Steroid resistance of airway type 2 innate lymphoid cells from patients with severe asthma: The role of thymic stromal lymphopoietin. J. Allergy Clin. Immunol. 141, 257–268.e256 (2018).

    CAS  PubMed  Google Scholar 

  65. Gauvreau, G. M. et al. Effects of an anti-TSLP antibody on allergen-induced asthmatic responses. N. Engl. J. Med. 370, 2102–2110 (2014).

    PubMed  Google Scholar 

  66. Corren, J. et al. Tezepelumab in Adults with Uncontrolled Asthma. N. Engl. J. Med. 377, 936–946 (2017). Ref. 66 provided clinical trial data showing that blockade of TSLP is effective in both T H2-high asthmatics and T H2-low asthmatics.

    CAS  PubMed  Google Scholar 

  67. Uller, L. & Persson, C. Viral induced overproduction of epithelial TSLP: role in exacerbations of asthma and COPD? J. Allergy Clin. Immunol. 142, 712 (2018).

    CAS  PubMed  Google Scholar 

  68. Israel, E. & Reddel, H. K. Severe and difficult-to-treat asthma in adults. N. Engl. J. Med. 377, 965–976 (2017).

    CAS  PubMed  Google Scholar 

  69. Ziegler, S. F. & Artis, D. Sensing the outside world: TSLP regulates barrier immunity. Nat. Immunol. 11, 289–293 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Binnewies, M. et al. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat. Med. 24, 541–550 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Loose, D. & Van de Wiele, C. The immune system and cancer. Cancer Biother. Radiopharm. 24, 369–376 (2009).

    CAS  PubMed  Google Scholar 

  72. Aspord, C. et al. Breast cancer instructs dendritic cells to prime interleukin 13-secreting CD4+ T cells that facilitate tumor development. J. Exp. Med. 204, 1037–1047 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. De Monte, L. et al. Intratumor T helper type 2 cell infiltrate correlates with cancer-associated fibroblast thymic stromal lymphopoietin production and reduced survival in pancreatic cancer. J. Exp. Med. 208, 469–478 (2011). Refs. 73 and 79 demonstrated a pro-tumor role for TSLP in human cancer.

    PubMed  PubMed Central  Google Scholar 

  74. Brunetto, E. et al. The IL-1/IL-1 receptor axis and tumor cell released inflammasome adaptor ASC are key regulators of TSLP secretion by cancer associated fibroblasts in pancreatic cancer. J. Immunother. Cancer 7, 45 (2019).

    PubMed  PubMed Central  Google Scholar 

  75. Xie, F. et al. Cervical carcinoma cells stimulate the angiogenesis through TSLP promoting growth and activation of vascular endothelial cells. Am. J. Reprod. Immunol. 70, 69–79 (2013).

    CAS  PubMed  Google Scholar 

  76. Barooei, R., Mahmoudian, R. A., Abbaszadegan, M. R., Mansouri, A. & Gholamin, M. Evaluation of thymic stromal lymphopoietin (TSLP) and its correlation with lymphatic metastasis in human gastric cancer. Med. Oncol. 32, 217 (2015).

    PubMed  Google Scholar 

  77. Xu, L. et al. Overexpression of thymic stromal lymphopoietin is correlated with poor prognosis in epithelial ovarian carcinoma. Biosci. Rep. 39, BSR20190116 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Watanabe, J., Saito, H., Miyatani, K., Ikeguchi, M. & Umekita, Y. TSLP expression and high serum TSLP level indicate a poor prognosis in gastric cancer patients. Yonago Acta Med. 58, 137–143 (2015).

    PubMed  PubMed Central  Google Scholar 

  79. Pedroza-Gonzalez, A. et al. Thymic stromal lymphopoietin fosters human breast tumor growth by promoting type 2 inflammation. J. Exp. Med. 208, 479–490 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Wu, T. C. et al. IL1 receptor antagonist controls transcriptional signature of inflammation in patients with metastatic breast cancer. Cancer Res. 78, 5243–5258 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Olkhanud, P. B. et al. Thymic stromal lymphopoietin is a key mediator of breast cancer progression. J. Immunol. 186, 5656–5662 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Aslakson, C. J. & Miller, F. R. Selective events in the metastatic process defined by analysis of the sequential dissemination of subpopulations of a mouse mammary γtumor. Cancer Res. 52, 1399–1405 (1992).

    CAS  PubMed  Google Scholar 

  83. Demehri, S. et al. Thymic stromal lymphopoietin blocks early stages of breast carcinogenesis. J. Clin. Invest. 126, 1458–1470 (2016).

    PubMed  PubMed Central  Google Scholar 

  84. Guy, C. T., Cardiff, R. D. & Muller, W. J. Induction of mammary tumors by expression of polyomavirus middle T oncogene: a transgenic mouse model for metastatic disease. Mol. Cell. Biol. 12, 954–961 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Ghirelli, C. et al. No evidence for TSLP pathway activity in human breast cancer. OncoImmunology 5, e1178438 (2016).

    PubMed  PubMed Central  Google Scholar 

  86. Kuan, E. L. & Ziegler, S. F. A tumor-myeloid cell axis, mediated via the cytokines IL-1α and TSLP, promotes the progression of breast cancer. Nat. Immunol. 19, 366–374 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Takahashi, N. et al. Thymic stromal chemokine TSLP acts through Th2 cytokine production to induce cutaneous T-cell lymphoma. Cancer Res. 76, 6241–6252 (2016).

    CAS  PubMed  Google Scholar 

  88. Demehri, S. et al. Elevated epidermal thymic stromal lymphopoietin levels establish an antitumor environment in the skin. Cancer Cell 22, 494–505 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Di Piazza, M., Nowell, C. S., Koch, U., Durham, A. D. & Radtke, F. Loss of cutaneous TSLP-dependent immune responses skews the balance of inflammation from tumor protective to tumor promoting. Cancer Cell 22, 479–493 (2012). Refs. 88 and 89 showed that TSLP expression in the skin is anti-tumor, unlike what had been seen for TSLP in tumors at other sites.

    PubMed  Google Scholar 

  90. Mullighan, C. G. The molecular genetic makeup of acute lymphoblastic leukemia. Hematology 2012, 389–396 (2012).

    PubMed  Google Scholar 

  91. Cobaleda, C. & Sánchez-García, I. B-cell acute lymphoblastic leukaemia: towards understanding its cellular origin. BioEssays 31, 600–609 (2009).

    PubMed  Google Scholar 

  92. Pui, C. H., Robison, L. L. & Look, A. T. Acute lymphoblastic leukaemia. Lancet 371, 1030–1043 (2008).

    CAS  PubMed  Google Scholar 

  93. Pui, C. H., Relling, M. V. & Downing, J. R. Acute lymphoblastic leukemia. N. Engl. J. Med. 350, 1535–1548 (2004).

    CAS  PubMed  Google Scholar 

  94. Roberts, K. G. et al. Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia. Cancer Cell 22, 153–166 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Yoda, A. et al. Functional screening identifies CRLF2 in precursor B-cell acute lymphoblastic leukemia. Proc. Natl Acad. Sci. USA 107, 252–257 (2010).

    CAS  PubMed  Google Scholar 

  96. Mullighan, C. G. et al. Rearrangement of CRLF2 in B-progenitor- and Down syndrome-associated acute lymphoblastic leukemia. Nat. Genet. 41, 1243–1246 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Russell, L. J. et al. Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia. Blood 114, 2688–2698 (2009). Refs. 96 and 97 showed that inversions and rearrangements of TSLPR in humans that lead to increased TSLPR expression are involved in a form of Ph-like pre-B cell lymphocytic leukemia.

    CAS  PubMed  Google Scholar 

  98. Ensor, H. M. et al. Demographic, clinical, and outcome features of children with acute lymphoblastic leukemia and CRLF2 deregulation: results from the MRC ALL97 clinical trial. Blood 117, 2129–2136 (2011).

    CAS  PubMed  Google Scholar 

  99. Hertzberg, L. et al. Down syndrome acute lymphoblastic leukemia, a highly heterogeneous disease in which aberrant expression of CRLF2 is associated with mutated JAK2: a report from the International BFM Study Group. Blood 115, 1006–1017 (2010).

    CAS  PubMed  Google Scholar 

  100. Malinge, S. et al. Novel activating JAK2 mutation in a patient with Down syndrome and B-cell precursor acute lymphoblastic leukemia. Blood 109, 2202–2204 (2007).

    CAS  PubMed  Google Scholar 

  101. Harvey, R. C. et al. Rearrangement of CRLF2 is associated with mutation of JAK kinases, alteration of IKZF1, Hispanic/Latino ethnicity, and a poor outcome in pediatric B-progenitor acute lymphoblastic leukemia. Blood 115, 5312–5321 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Roll, J. D. & Reuther, G. W. CRLF2 and JAK2 in B-progenitor acute lymphoblastic leukemia: a novel association in oncogenesis. Cancer Res. 70, 7347–7352 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Chapiro, E. et al. Activating mutation in the TSLPR gene in B-cell precursor lymphoblastic leukemia. Leukemia 24, 642–645 (2010).

    CAS  PubMed  Google Scholar 

  104. Shochat, C. et al. Gain-of-function mutations in interleukin-7 receptor-α (IL7R) in childhood acute lymphoblastic leukemias. J. Exp. Med. 208, 901–908 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Qin, H. et al. Eradication of B-ALL using chimeric antigen receptor-expressing T cells targeting the TSLPR oncoprotein. Blood 126, 629–639 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Iseki, M. et al. Thymic stromal lymphopoietin (TSLP)-induced polyclonal B-cell activation and autoimmunity are mediated by CD4+ T cells and IL-4. Int. Immunol. 24, 183–195 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Volpe, E. et al. Thymic stromal lymphopoietin links keratinocytes and dendritic cell-derived IL-23 in patients with psoriasis. J. Allergy Clin. Immunol. 134, 373–381 (2014).

    CAS  PubMed  Google Scholar 

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  1. Department of Medicine and Department of Pediatrics, Division of Allergy and Clinical Immunology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Jonathan Corren

  2. Immunology Program, Benaroya Research Institute, Seattle, WA, USA

    Steven F. Ziegler

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Corren, J., Ziegler, S.F. TSLP: from allergy to cancer. Nat Immunol 20, 1603–1609 (2019). https://doi.org/10.1038/s41590-019-0524-9

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