IL23R on myeloid cells is involved in murine pulmonary granuloma formation. (3rd September 2021)

• Record Type: Journal Article
• Authors: Schreiber, Tina; Falk-Paulsen, Maren; Kuiper, Jan; Aden, Konrad; Noth, Rainer; Gisch, Nicolas; Schreiber, Stefan; Rosenstiel, Philip; Bewig, Burkhard
• Is Part Of: Experimental lung research. Volume 47:Number 7(2021)
• Page Start: 344
• Page End: 353
• Publication Date: 2021-09-03
• Subjects: Inflammatory granulomatous lung disease -- sarcoidosis -- IL23R -- myeloid cells; Lungs -- Periodicals; Lungs -- Diseases -- Periodicals; Lung Diseases; Lung -- physiology; Respiratory System; 616.24
• DOI: 10.1080/01902148.2021.1962433
• Languages: English
• ISSNs: 0190-2148

Abstract

Abstract: Purpose of the Study: The involvement of the IL-23/IL23R pathway is well known in the disease pathogenesis of sarcoidosis and other inflammatory diseases. To date, the pathogenic mechanism of IL-23 is most notably described on CD4 + Th17 lymphocytes. However, the function of the IL23R on myeloid cells in sarcoidosis is poorly understood. Thus, the aim of the study is to investigate the role of the IL23R on myeloid cell in pulmonary granuloma formation. Methods: We generated IL23RLysMCre mice lacking the IL23R gene in myeloid cells. The importance of IL23R in myeloid cells for the development of sarcoidosis was studied in a mouse model of inflammatory lung granuloma formation through embolization of PPD from Mycobacterium bovis -coated Sepharose beads into previously PPD-immunized mice. In addition the function of IL23R on myeloid cells was studied in LPS or IFNγ stimulated BMDMs and BMDCs. The mRNA and protein expression levels of relevant cytokines were analyzed by RT-PCR (TaqMan) and ELISA. The composition of immune cells in BALF was quantified by flow cytometry and alteration in granuloma sizes were observed by H&E stained lung sections. Results: Mycobacterium Ag-elicted pulmonary granulomas tend to be smaller in IL23RLysMCre mice and NF-κB dependent Th1 cytokines in the murine lungs are reduced compared to wildtype mice. In line, we observed that IL23R-deficient bone marrow-derived macrophages show a reduced production of Th1 cytokines after LPS stimulation. Conclusion: We here for the first time demonstrate a role for IL23R on myeloid cells in pulmonary inflammation and granuloma formation. Our findings provide essential insights in the pathogenesis of inflammatory lung diseases like sarcoidosis, which might be useful for the development of novel therapeutics targeting distinct immunological pathways like IL-23/IL23R.