Interaction between human mature adipocytes and lymphocytes induces T-cell proliferation.
OBJECTIVE
Adipose tissue is a critical organ that plays a major role in energy balance regulation and the immune response through intricate signals.


METHODS
We report on the inter-relation between mature adipocytes and lymphocytes in terms of adipocyte-derived T-cell chemo-attractants and adipocyte metabolic effects on lymphocytes.


RESULTS
During the culture time, mature adipocytes changed their structural and functional properties into de-differentiated cells. Isolated mature adipocytes expressed significantly higher levels of CIITA, major histocompatibility complex II (human leukocyte antigen [HLA]-DR) and costimulatory signal molecule CD80 compared with adipocytes after the de-differentiation process. Moreover, human leukocyte antigen-G, which may prevent the immune responses of mesenchymal stromal cells, was expressed at lower level in mature adipocytes compared with de-differentiated adipocytes. In line with these molecular data, functional results showed different immunoregulatory properties between adipocytes before and after the de-differentiation process. Mature adipocytes stimulated the proliferation of total lymphocytes and immunoselected cell populations CD3+, CD4+ and CD8+ in a direct contact-dependent way that involved the major histocompatibility complex I and II pathways. Moreover, adipocytes secreted potential chemo-attractant factors, but data showed that adipocyte-derived culture medium was not sufficient to activate lymphocyte proliferation, suggesting that a direct contact between adipocytes and immune cells was needed. However, specific mature adipocyte cytokines enhanced lymphocyte proliferation in a mixed lymphocyte reaction.


CONCLUSIONS
In conclusion, cross-talk occurs between adipocytes and lymphocytes within adipose tissue involving T-cell chemo-attraction by mature adipocytes. Our findings, together with current observations in the field, provide a rationale to identify adipocyte-lymphocyte cross-talk that instigates adipose inflammation.
Clinica di Ematologia, Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Ancona, Italy. Electronic address: a.poloni@univpm.it.
Antonella
A
Poloni
Clinica di Ematologia, Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Ancona, Italy.
Giulia
G
Maurizi
Clinica di Ematologia, Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Ancona, Italy.
Marco
M
Ciarlantini
Clinica di Ematologia, Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Ancona, Italy.
Martina
M
Medici
Clinica di Ematologia, Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Ancona, Italy.
Domenico
D
Mattiucci
Clinica di Ematologia, Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Ancona, Italy.
Stefania
S
Mancini
Clinica Chirurgia del Pancreas, Università Politecnica delle Marche, Ospedali Riuniti, Ancona, Italy.
Angela
A
Maurizi
Clinica Chirurgia del Pancreas, Università Politecnica delle Marche, Ospedali Riuniti, Ancona, Italy.
Massimo
M
Falconi
Clinica di Ematologia, Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Ancona, Italy.
Attilio
A
Olivieri
Clinica di Ematologia, Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Ancona, Italy.
Pietro
P
Leoni
D017667:Adipocytes / Q000166:cytology / Q000276:immunology*; D000273:Adipose Tissue / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D000368:Aged; D000369:Aged, 80 and over; D018122:B7-1 Antigen / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D006684:HLA-DR Antigens / Q000276:immunology; D059951:HLA-G Antigens / Q000096:biosynthesis; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D059630:Mesenchymal Stem Cells / Q000276:immunology; D008875:Middle Aged; D009687:Nuclear Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D015534:Trans-Activators / Q000276:immunology
D018122:B7-1 Antigen; D016207:Cytokines; D006684:HLA-DR Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators
T-cell activation; de-differentiated adipocytes; inflammation; mature adipocytes