title: Mast cells and Th17 cells contribute to the lymphoma-associated pro-inflammatory microenvironment of angioimmunoblastic T-cell lymphoma.
abstract: Reports focusing on the immunological microenvironment of peripheral T-cell lymphomas (PTCL) are rare. Here we studied the reciprocal contribution of regulatory (Treg) and interleukin-17-producing (Th17) T-cells to the composition of the lymphoma-associated microenvironment of angioimmunoblastic T-cell lymphoma (AITL) and PTCL not otherwise specified on tissue microarrays from 30 PTCLs not otherwise specified and 37 AITLs. We found that Th17 but not Treg cells were differently represented in the two lymphomas and correlated with the amount of mast cells (MCs) and granulocytes, which preferentially occurred in the cellular milieu of AITL cases. We observed that MCs directly synthesized interleukin-6 and thus contribute to the establishment of a pro-inflammatory, Th17 permissive environment in AITL. We further hypothesized that the AITL clone itself could be responsible for the preferential accumulation of MCs at sites of infiltration through the synthesis of CXCL-13 and its interaction with the CXCR3 and CXCR5 receptors expressed on MCs. Consistent with this hypothesis, we observed MCs efficiently migrating in response to CXCL-13. On these bases, we conclude that MCs have a role in molding the immunological microenvironment of AITL toward the maintenance of pro-inflammatory conditions prone to Th17 generation and autoimmunity.
authors.affiliation: Department of Human Pathology, University of Palermo, Palermo, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Tripodo
authors.forename: Giorgia
authors.initials: G
authors.lastname: Gri
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Piccaluga
authors.forename: Barbara
authors.initials: B
authors.lastname: Frossi
authors.forename: Carla
authors.initials: C
authors.lastname: Guarnotta
authors.forename: Silvia
authors.initials: S
authors.lastname: Piconese
authors.forename: Giovanni
authors.initials: G
authors.lastname: Franco
authors.forename: Valeria
authors.initials: V
authors.lastname: Vetri
authors.forename: Carlo Ennio
authors.initials: CE
authors.lastname: Pucillo
authors.forename: Ada Maria
authors.initials: AM
authors.lastname: Florena
authors.forename: Mario Paolo
authors.initials: MP
authors.lastname: Colombo
authors.forename: Stefano Aldo
authors.initials: SA
authors.lastname: Pileri
mesh_terms: D000818:Animals; D054382:Chemokine CXCL13 / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000276:immunology; D020869:Gene Expression Profiling; D006801:Humans; D007119:Immunoblastic Lymphadenopathy / Q000276:immunology* / Q000473:pathology; D007249:Inflammation / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D016399:Lymphoma, T-Cell / Q000276:immunology* / Q000473:pathology; D008407:Mast Cells / Q000276:immunology*; D046228:Microarray Analysis; D058504:Th17 Cells / Q000276:immunology*; D059016:Tumor Microenvironment
chemical_list: D054382:Chemokine CXCL13; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D020381:Interleukin-17; D015850:Interleukin-6