29 April 2019

IL-22-expressing CD4(+) AhR(+) T lymphocytes are associated with RANKL-mediated alveolar bone resorption during experimental periodontitis

DOI : 10.1111/jre.12654

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Cristian Cortez, PhD.

BACKGROUND AND OBJECTIVE: Over the past few years, the importance of

interleukin-22 (IL-22) and T-helper (Th)22 lymphocytes in the pathogenesis of

periodontitis has become apparent; however, there are still aspects that are not

addressed yet. Cells expressing IL-22 and aryl hydrocarbon receptor (AhR),

transcription factor master switch gene implicated in the differentiation and

function of Th22 lymphocytes, have been detected in periodontal tissues of

periodontitis-affected patients. In addition, IL-22 has been associated with

osteoclast differentiation and their bone resorptive activity in vitro. However,

the destructive potential of IL-22-expressing AhR+ Th22 lymphocytes over

periodontal tissues during periodontitis has not been demonstrated in vivo yet.

Therefore, this study aimed to analyze whether IL-22-expressing CD4+ AhR+ T

lymphocytes detected in periodontal lesions are associated with alveolar bone

resorption during experimental periodontitis.

MATERIAL AND METHODS: Using a murine model of periodontitis, the expression

levels of IL-22 and AhR, as well as the Th1-, Th2-, Th17- and T

regulatory-associated cytokines, were analyzed in periodontal lesions using

qPCR. The detection of CD4+ IL-22+ AhR+ T lymphocytes was analyzed in

periodontal lesions and cervical lymph nodes that drain these periodontal

lesions using flow cytometry. In addition, the expression of the

osteoclastogenic mediator called receptor activator of nuclear factor-κB ligand

(RANKL) was analyzed by qPCR, western blot, and immunohistochemistry. Finally,

alveolar bone resorption was analyzed using micro-computed tomography and

scanning electron microscopy, and the bone resorption levels were correlated

with IL-22 and RANKL expression.

RESULTS: Higher levels of IL-22, AhR, and RANKL, as well as IL-1β, IL-6, IL-12,

IL-17, IL-23, and TNF-α, were expressed in periodontal lesions of infected mice

compared with periodontal tissues of sham-infected and non-infected controls.

Similarly, high RANKL immunoreaction was observed in periodontal tissues of

infected mice; however, few or absent RANKL immunoreaction was observed in

controls. This association between RANKL and periodontal infection was ratified

by western blot. Furthermore, a higher detection of CD4+ IL-22+ AhR+ T

lymphocytes was found in periodontal lesions and cervical lymph nodes that drain

these periodontal lesions in infected mice compared with non-infected controls.

Finally, the increased IL-22 and RANKL expression showed positive correlation

between them and with the augmented alveolar bone resorption observed in

experimental periodontal lesions.

CONCLUSION: This study demonstrates the increase of IL-22-expressing CD4+ AhR+ T

lymphocytes in periodontitis-affected tissues and shows a positive correlation

between IL-22, RANKL expression, and alveolar bone resorption.

Participating Center Researchers

Host-Pathogen Interactions Laboratory

PhD in Sciences, mention Microbiology, Inmunology, and Parasitology, Universidade Federal de São Paulo, Brasil.


LEER MÁS
Edificio2

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