Interleukin-12 family cytokines and sarcoidosis

Abstract

Sarcoidosis is a systemic granulomatous disease predominantly affecting the lungs. It is believed to be caused by exposure to pathogenic antigens in genetically susceptible individuals but the causative antigen has not been identified. The formation of non-caseating granulomas at sites of ongoing inflammation is the key feature of the disease. Other aspects of the pathogenesis are peripheral T-cell anergy and disease progression to fibrosis. Many T-cell-associated cytokines have been implicated in the immunopathogenesis of sarcoidosis, but it is becoming apparent that IL-12 cytokine family members including IL-12, IL-23, IL-27, and IL-35 are also involved. Although the members of this unique cytokine family are heterodimers of similar subunits, their biological functions are very diverse. Whilst IL-23 and IL-12 are pro-inflammatory regulators of Th1 and Th17 responses, IL-27 is bidirectional for inflammation and the most recent family member IL-35 is inhibitory. This review will discuss the current understanding of etiology and immunopathogenesis of sarcoidosis with a specific focus on the bidirectional impact of IL-12 family cytokines on the pathogenesis of sarcoidosis.

Exploring the dynamic changes between pulmonary and cutaneous sarcoidosis based on gene expression

“…Consistent with our findings, previous researches have reported that persistent stimulation of the immune system plays a major role in granuloma formation and maintenance [26,34]. Some immunerelated cells such as macrophages, dendritic cells, lymphocytes and regulatory T cells, as well as immune-related factors are all closely involved in the cellular and molecular mechanisms of granuloma formation [8,19,35] and in the immune-pathogenesis of sarcoidosis [34]. Recent research indicated that immune-relevant factors such as IL-33 are important factors in sarcoidosis, making them potential biomarkers [36,37].…”

IL‐35: A potential therapeutic target for controlling hepatitis B virus infection

“…Despite the common structures of the cytokines and receptors as well as the downstream signaling components, the biological activities of the IL‐12 family members are, to some extent, quite diverse . A consensus has been reached that IL‐12 and IL‐23 are mainly proinflammatory and pro‐stimulatory cytokines that play vital roles in the differentiation of T helper (Th) 1 and Th17 cells, respectively .…”

Interleukin‐35 in immune‐related diseases: protection or destruction

“…All four are heterodimers: P35 and P40 subunits heterodimerize to form IL‐12, P40 and P19 form IL‐23, EBI3 and P28 form IL‐27, and EBI3 and P35 form IL‐35 (Fig. ) . EBI3 is widely expressed in B lymphocytes and tissues, including the spleen and tonsils transformed by the Epstein–Barr virus .…”

“…1). 5,[16][17][18][19] EBI3 is widely expressed in B lymphocytes and tissues, including the spleen and tonsils transformed by the Epstein-Barr virus. 14 EBI3 plays a critical role in the immune response by down-regulating the expression of transcription factor RORct in T helper type 17 (Th17) cells and inhibiting inflammatory response.…”