Mast cells and Th17 cells contribute to the lymphoma-associated pro-inflammatory microenvironment of angioimmunoblastic T-cell lymphoma.
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.
Tripodo
Claudio
C
Department of Human Pathology, University of Palermo, Palermo, Italy.
Gri
Giorgia
G
Piccaluga
Pier Paolo
PP
Frossi
Barbara
B
Guarnotta
Carla
C
Piconese
Silvia
S
Franco
Giovanni
G
Vetri
Valeria
V
Pucillo
Carlo Ennio
CE
Florena
Ada Maria
AM
Colombo
Mario Paolo
MP
Pileri
Stefano Aldo
SA
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
D054382:Chemokine CXCL13; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D020381:Interleukin-17; D015850:Interleukin-6