M2 macrophages coexist with a Th1‐driven profile in periapical cysts

Abstract

Ribeiro CM, de Carli ML, Nonogaki S, Nogueira DA, Pereira AAC, Sperandio FF, Hanemann JAC. M2 macrophages coexist with a Th1-driven profile in periapical cysts. International Endodontic Journal, 51, e87-e93, 2018.Aim To evaluate the participation of both Th1 and Th2 responses in periapical cysts by assessing the presence of M2 macrophages, as well as acute IL-1 b, TNF-a and IL-6 cytokines. Methodology Twenty-four cases of periapical cysts were selected. Immuno-expressions of IL-1 b, IL-6, TNF-a and CD163 were analysed in the cystic capsules in both superficial and deeper regions. Data were analysed with paired Wilcoxon test and Spearman correlation coefficient (P ≤ 0.05). Results There was a higher expression of IL-1b, IL-6, TNF-a and M2 macrophages in the superficial region (P < 0.001) of cystic capsules. All acute cytokines had significant positive correlations amongst them regardless of the cystic capsule region. Regarding CD163, positive correlations occurred only with TNF-a (P = 0.007; r = 0.537) and IL-6 (P = 0.018; r = 0.478) in the superficial regions of the cystic capsule. Conclusions M2 macrophages participated actively in the inflammatory response of periapical cysts and correlated with the expression of certain acute Th1-related cytokines. This illustrates the coexistence of an acute and chronic Th2-driven immune response in these lesions. Although M2 macrophages favour the healing process, their presence is not sufficient for periapical cyst regression, once an acute active response has occurred due to an infectious stimuli.

Macrophages subpopulations in chronic periapical lesions according to clinical and morphological aspects

“…This study found high levels of macrophages in small and initial lesions due to active antigenic stimuli. Macrophage subpopulations have been previously described 6,13 , but associations between these cells and TNF-α, as well as comparisons with clinical information, were not available until now.…”

“…Previous studies have suggested that macrophage polarization contributes to the formation, development, and growth of both RCs and PGs 6,13 . However, information regarding the specific location of M1 and M2 macrophages, the phenotypes associated with TNF-α in RC epithelium, and the relationship of these cells with clinical aspects and lesion stage and size have not yet been investigated.…”

Effects of cigarette smoke inhalation on the immune‐inflammatory profile of experimental apical periodontitis in rats

“…Despite the tendency towards the M1 phenotype, we found M2 macrophages in the evaluated groups (C, S, AP and APS), evincing their co‐performance. A study assessing periapical cysts in humans found similar data, observing the presence of M2 macrophages and the pro‐inflammatory cytokines TNF‐α, IL‐1β and IL‐6 (which modulate M1 macrophage polarization) at the same site (Ribeiro et al, 2018). Another study evaluating root cysts in humans' primary and permanent teeth also showed M1 and M2 macrophage in its samples, but with a predominance of M2 macrophages (Bertasso et al, 2020).…”

“…However, the M2 role may also relate to the formation and maintenance of fibrous capsules to contain lesion progression. M2 macrophages have been found in superficial cystic capsules in humans (Ribeiro et al, 2018).…”

“…Despite the relevant information in the field, note that the role and balance of M1 and M2 macrophages in chronic AP progression are yet to be determined. For example, TNF‐α, IL‐1β and IL‐6 with M2 macrophages have been found in human periapical cysts (Ribeiro et al, 2018). Veloso et al (2020) analysed 110 samples of apical periodontitis in humans by flow cytometry to identify M1 and M2 profiles, finding that symptomatic lesions show a weaker differentiation into M2 phenotypes and greater M1 activation and IL‐6 and IL‐23 expression.…”