The IL-31/IL-31 receptor axis

General features and role in tumor microenvironment

Elisa Ferretti, Anna Corcione, Vito Pistoia

Research output: Contribution to journalReview article

11 Citations (Scopus)

Abstract

IL-31 is a recently identified cytokine with a well-defined role in the pathogenesis of pruritus. IL-31, whose production is induced by IL-4 and IL-33, binds a heterodi-meric receptor (R) composed of the exclusive IL-31RA chain and the shared oncostatin M R. Signaling through the IL-31R involves the MAPK, PI3K/AKT and Jak/STAT pathways. Different variants and isoforms of IL-31RA with different signaling activities have been identified. IL-31 is produced predominantly by circulating Th2 lymphocytes and skin-homing CLA+CD45RO+ T cells. Studies in humans have demonstrated a pathogenic role for IL-31 in atopic dermatitis and allergic asthma. The first demonstration of the involvement of the IL-31/IL-31R axis in cancer came from studies in patients with mycosis fungoides/Sézary syndrome, the most frequent, cutaneous T cell lymphoma. Tumor cells were shown to produce IL-31, whose serum levels correlated with pruritus intensity. Follicular lymphoma (FL) B cells and their counterparts—germinal center B cells—produced IL-31 and expressed IL-31R, which signaled in the former, but not the latter, cells. IL-31 released in association with microvesicles promoted tumor growth through autocrine/paracrine loops. Malignant mast cells from patients with mastocytosis or Philadelphia-negative myeloproliferative disorder produced IL-31, which contributed to pruritus pathogenesis. Finally, patients with endometrial carcinoma displayed high serum levels of IL-31 and IL-33, which may represent promising disease biomarkers. Targeting strategies for the IL-31/IL-31R axis have been developed, including the CIMM331 humanized anti-human IL-31RA antibody recently tested in a phase I/Ib study.

Original languageEnglish
Pages (from-to)711-717
Number of pages7
JournalJournal of Leukocyte Biology
Volume102
Issue number3
DOIs
Publication statusPublished - Sep 1 2017

Fingerprint

Tumor Microenvironment
Pruritus
Oncostatin M
Mastocytosis
Cutaneous T-Cell Lymphoma
Myeloproliferative Disorders
Neoplasms
Mycosis Fungoides
Follicular Lymphoma
Atopic Dermatitis
Endometrial Neoplasms
Serum
Phosphatidylinositol 3-Kinases
Mast Cells
Interleukin-4
Protein Isoforms
B-Lymphocytes
Asthma
Biomarkers
Lymphocytes

Keywords

  • Allergy
  • Cancer growth
  • Cytokine

ASJC Scopus subject areas

  • Immunology
  • Cell Biology

Cite this

The IL-31/IL-31 receptor axis : General features and role in tumor microenvironment. / Ferretti, Elisa; Corcione, Anna; Pistoia, Vito.

In: Journal of Leukocyte Biology, Vol. 102, No. 3, 01.09.2017, p. 711-717.

Research output: Contribution to journalReview article

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abstract = "IL-31 is a recently identified cytokine with a well-defined role in the pathogenesis of pruritus. IL-31, whose production is induced by IL-4 and IL-33, binds a heterodi-meric receptor (R) composed of the exclusive IL-31RA chain and the shared oncostatin M R. Signaling through the IL-31R involves the MAPK, PI3K/AKT and Jak/STAT pathways. Different variants and isoforms of IL-31RA with different signaling activities have been identified. IL-31 is produced predominantly by circulating Th2 lymphocytes and skin-homing CLA+CD45RO+ T cells. Studies in humans have demonstrated a pathogenic role for IL-31 in atopic dermatitis and allergic asthma. The first demonstration of the involvement of the IL-31/IL-31R axis in cancer came from studies in patients with mycosis fungoides/S{\'e}zary syndrome, the most frequent, cutaneous T cell lymphoma. Tumor cells were shown to produce IL-31, whose serum levels correlated with pruritus intensity. Follicular lymphoma (FL) B cells and their counterparts—germinal center B cells—produced IL-31 and expressed IL-31R, which signaled in the former, but not the latter, cells. IL-31 released in association with microvesicles promoted tumor growth through autocrine/paracrine loops. Malignant mast cells from patients with mastocytosis or Philadelphia-negative myeloproliferative disorder produced IL-31, which contributed to pruritus pathogenesis. Finally, patients with endometrial carcinoma displayed high serum levels of IL-31 and IL-33, which may represent promising disease biomarkers. Targeting strategies for the IL-31/IL-31R axis have been developed, including the CIMM331 humanized anti-human IL-31RA antibody recently tested in a phase I/Ib study.",
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