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 language | English |
|---|---|
| Pages (from-to) | 711-717 |
| Number of pages | 7 |
| Journal | Journal of Leukocyte Biology |
| Volume | 102 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Sep 1 2017 |
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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 journal › Review article
}
TY - JOUR
T1 - The IL-31/IL-31 receptor axis
T2 - General features and role in tumor microenvironment
AU - Ferretti, Elisa
AU - Corcione, Anna
AU - Pistoia, Vito
PY - 2017/9/1
Y1 - 2017/9/1
N2 - 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.
AB - 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.
KW - Allergy
KW - Cancer growth
KW - Cytokine
UR - http://www.scopus.com/inward/record.url?scp=85028658072&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85028658072&partnerID=8YFLogxK
U2 - 10.1189/jlb.3MR0117-033R
DO - 10.1189/jlb.3MR0117-033R
M3 - Review article
VL - 102
SP - 711
EP - 717
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 3
ER -