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Horm Metab Res 2013; 45(10): 741-747
DOI: 10.1055/s-0033-1348221
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

CD40L Stimulates the Crosstalk Between Adipocytes and Inflammatory Cells

A. Chatzigeorgiou
1   Department of Internal Medicine III, University of Dresden, ­Dresden, Germany
2   Institute of Physiology, University of Dresden, Dresden, Germany
3   Paul-Langerhans Institute Dresden, German Center for Diabetes Research (DZD), Dresden, Germany
,
J. Phieler
1   Department of Internal Medicine III, University of Dresden, ­Dresden, Germany
2   Institute of Physiology, University of Dresden, Dresden, Germany
3   Paul-Langerhans Institute Dresden, German Center for Diabetes Research (DZD), Dresden, Germany
,
J. Gebler
1   Department of Internal Medicine III, University of Dresden, ­Dresden, Germany
2   Institute of Physiology, University of Dresden, Dresden, Germany
,
S. R. Bornstein
1   Department of Internal Medicine III, University of Dresden, ­Dresden, Germany
3   Paul-Langerhans Institute Dresden, German Center for Diabetes Research (DZD), Dresden, Germany
,
T. Chavakis
1   Department of Internal Medicine III, University of Dresden, ­Dresden, Germany
2   Institute of Physiology, University of Dresden, Dresden, Germany
3   Paul-Langerhans Institute Dresden, German Center for Diabetes Research (DZD), Dresden, Germany
4   Institute for Clinical Chemistry and Laboratory Medicine, University of Dresden, Dresden, Germany
› Author Affiliations
Further Information

Publication History

received 05 October 2012

accepted 14 May 2012

Publication Date:
05 August 2013 (online)

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Abstract

Macrophages and lymphocytes are implicated in obesity-related adipose tissue inflammation via interactions with adipocytes. Co-stimulatory systems, especially the CD40-CD40L system, play an important role in T cell activation and inflammatory reactions. CD40L was recently shown to promote adipose tissue inflammation in vivo, yet, the mechanisms underlying its function in the intercellular communication between inflammatory cells and adipocytes remain not entirely clear. Here we found that adipocyte stimulation with CD40L increased the expression of CD40, as well as of chemokines, such as MCP-1, CCL4, or CCL5, whereas adipocyte CD40 expression was also stimulated by TNF but not palmitate. Moreover, conditioned media of CD40L-pretreated adipocytes provoked elevated migration of mononuclear cells and increased the expression of inflammatory genes in bone marrow derived mononuclear phagocytes (BMDM) shifting them to an M1-like pro-inflammatory phenotype. Nonetheless, the CD40/CD40L interaction did not contribute to the adhesion between adipocytes and T cells. Together, CD40L stimulates adipocyte chemokine expression, thereby attracting monocytes/macrophages into the adipose tissue. Moreover, CD40L stimulation of adipocytes likely promotes macrophage M1 polarization in the adipose tissue and thereby perpetuation of adipose tissue inflammation.

Key words

co-stimulation - T cells - macrophages - inflammation - obesity - CD40
 

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