Universität zu Köln

Brahler, Sebastian, Zinselmeyer, Bernd H., Raju, Saravanan, Nitschke, Maximilian, Suleiman, Hani, Saunders, Brian T., Johnson, Michael W., Boehner, Alexander M. C., Viehmann, Susanne F., Theisen, Derek J., Kretzer, Nicole M., Briseno, Carlos G., Zaitsev, Konstantin ORCID: 0000-0003-3749-0886, Ornatsky, Olga, Chang, Qing, Carrero, Javier A., Kopp, Jeffrey B., Artyomov, Maxim N., Kurts, Christian, Murphy, Kenneth M., Miner, Jeffrey H. and Shaw, Andrey S. (2018). Opposing Roles of Dendritic Cell Subsets in Experimental GN. J. Am. Soc. Nephrol., 29 (1). S. 138 - 155. WASHINGTON: AMER SOC NEPHROLOGY. ISSN 1533-3450

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Abstract

Dendritic cells (DCs) are thought to form a dendritic network across barrier surfaces and throughout organs, including the kidney, to perform an important sentinel function. However, previous studies of DC function used markers, such as CD11c or CX3CR1, that are not unique to DCs. Here, we evaluated the role of DCs in renal inflammation using a CD11c reporter mouse line and two mouse lines with DC-specific reporters, Zbtb46-GFP and Snx22-GFP. Multiphoton microscopy of kidney sections confirmed that most of the dendritically shaped CD11c(+) cells forming a network throughout the renal interstitium expressed macrophage-specific markers. In contrast, DCs marked by Zbtb46-GFP or Snx22-GFP were less abundant, concentrated around blood vessels, and round in shape. We confirmed this pattern of localization using imaging mass cytometry. Motility measurements showed that resident macrophages were sessile, whereas DCs were motile before and after inflammation. Although uninflamed glomeruli rarely contained DCs, injury with nephrotoxic antibodies resulted in accumulation of ZBTB46(+) cells in the periglomerular region. ZBTB46 identifies all classic DCs, which can be categorized into two functional subsets that express either CD103 or CD11b. Depletion of ZBTB46(+) cells attenuated the antibody-induced kidney injury, whereas deficiency of the CD103(+) subset accelerated injury through a mechanism that involved increased neutrophil infiltration. RNA sequencing 7 days after nephrotoxic antibody injection showed that CD11b(+) DCs expressed the neutrophil-attracting cytokine CXCL2, whereas CD103(+) DCs expressed high levels of several anti-inflammatory genes. These results provide new insights into the distinct functions of the two major DC subsets in glomerular inflammation.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Brahler, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Zinselmeyer, Bernd H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Raju, Saravanan UNSPECIFIED UNSPECIFIED UNSPECIFIED Nitschke, Maximilian UNSPECIFIED UNSPECIFIED UNSPECIFIED Suleiman, Hani UNSPECIFIED UNSPECIFIED UNSPECIFIED Saunders, Brian T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Johnson, Michael W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Boehner, Alexander M. C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Viehmann, Susanne F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Theisen, Derek J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kretzer, Nicole M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Briseno, Carlos G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Zaitsev, Konstantin UNSPECIFIED orcid.org/0000-0003-3749-0886 UNSPECIFIED Ornatsky, Olga UNSPECIFIED UNSPECIFIED UNSPECIFIED Chang, Qing UNSPECIFIED UNSPECIFIED UNSPECIFIED Carrero, Javier A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kopp, Jeffrey B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Artyomov, Maxim N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kurts, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Murphy, Kenneth M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Miner, Jeffrey H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Shaw, Andrey S. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-204817
DOI:	10.1681/ASN.2017030270
Journal or Publication Title:	J. Am. Soc. Nephrol.
Volume:	29
Number:	1
Page Range:	S. 138 - 155
Date:	2018
Publisher:	AMER SOC NEPHROLOGY
Place of Publication:	WASHINGTON
ISSN:	1533-3450
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language LANGERHANS CELLS; IN-VIVO; BONE-MARROW; NEPHROTOXIC NEPHRITIS; MASS CYTOMETRY; CRESCENTIC GN; T-CELLS; KIDNEY; MACROPHAGES; EXPRESSION Multiple languages Urology & Nephrology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/20481