A Role for CD154, the CD40 Ligand, in Granulomatous Inflammation

Abstract

Granulomatous inflammation is a distinctive form of chronic inflammation in which predominant cells include macrophages, epithelioid cells, and multinucleated giant cells. Mechanisms regulating granulomatous inflammation remain ill-understood. CD154, the ligand of CD40, is a key mediator of inflammation. CD154 confers a proinflammatory phenotype to macrophages and controls several macrophagic functions. Here, we studied the contribution of CD154 in a mouse model of toxic liver injury with carbon tetrachloride and a model of absorbable suture graft. In both models, granulomas are triggered in response to endogenous persistent liver calcified necrotic lesions or by grafted sutures. CD154-deficient mice showed delayed clearance of carbon tetrachloride-induced liver calcified necrotic lesions and impaired progression of suture-induced granuloma. In vitro, CD154 stimulated phagocytosis of opsonized erythrocytes by macrophages, suggesting a potential mechanism for the altered granulomatous inflammation in CD154KO mice. These results suggest that CD154 may contribute to the natural history of granulomatous inflammation.

Suture granulomas developing after the treatment of oral squamous cell carcinoma

“…Yamamoto et al reported that the development of a foreign body granuloma may be associated with an immunoreaction of macrophages [ 2 ]. Immunohistochemical examination in the present case showed several CD68-positive cells surrounding the suture material; this finding supported those of a previous study, where several cells positive for the anti-CD68 antibody were observed to surround the foreign body [ 9 ]. Radiation may enhance the immunoreaction of several types of immune cells in the radiation field and promote the formation of granulation tissue in a short period of time.…”

Evaluation of monocyte subsets and markers of activation in leprosy reactions

“…We have found a higher expression of CD40 in PB patients presenting T1R when compared with PB subjects without reaction but no difference in MB patients with or without T2R. The CD40 interaction with its ligand CD154 is important to drive IL-12 production and development of cellular immunity against intracellular pathogens, but it is also involved in granulomatous inflammation [25]. Therefore, CD40 expression by monocytes in leprosy may be involved not only with protection mechanisms against M. leprae, but also in the development of T1R when at high levels.…”