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01-08-2018 | Original article

Semaphorin 7A in circulating regulatory T cells is increased in autosomal-dominant polycystic kidney disease and decreases with tolvaptan treatment

Authors: Yashang Lee, Katrina Lehmann Blount, Feng Dai, Siobhan Thompson, Jonathan Kaufman Scher, Sherrie Bitterman, Madeline Droher, Erica L. Herzog, Gilbert Moeckel, Anil Karihaloo, Neera K. Dahl

Published in: Clinical and Experimental Nephrology | Issue 4/2018

Abstract

Background

Semaphorin 7A (SEMA7A) is an immunomodulating protein implicated in lung and liver fibrosis. In autosomal-dominant polycystic kidney disease (ADPKD), the progressive expansion of renal cysts, inflammation, and subsequent renal fibrosis leads to end-stage renal disease (ESRD). SEMA7A may play a role in renal fibrosis and in ADPKD.

Methods

We evaluated Sema7a in a mouse model of renal fibrosis and determined the expression of SEMA7A in human ADPKD kidney. We analyzed SEMA7A expression on peripheral blood mononuclear cells (PBMCs), including CD45⁺ (leukocyte), CD14⁺(monocyte), CD4+ (T lymphocytes) and CD4⁺Foxp3⁺CD25⁺ [regulatory T lymphocytes (Tregs)] from 90 ADPKD patients (11 tolvaptan treated and 79 tolvaptan naïve), and 21 healthy volunteers, using a Fluorescence-Activated Cell Sorting (FACS).

Results

Sema7a is required for renal fibrosis. SEMA7A shows robust expression in ADPKD kidneys, localizing to cysts derived from distal tubules. SEMA7A is higher in circulating monocytes, but unchanged in CD4⁺ lymphocytes in ADPKD patients. The SEMA7A increase was detected early (stage 1 CKD) and seemed more prominent in patients with smaller kidneys (p = 0.09). Compared to tolvaptan-naïve ADPKD patients, those treated with tolvaptan showed reduced SEMA7A expression on monocytes, T lymphocytes, and Tregs, although the number of PBMCs was unchanged. After 1 month of tolvaptan treatment, SEMA7A expression on Tregs decreased.

Conclusions

SEMA7A shows potential as both a therapeutic target in mammalian kidney fibrosis and as a marker of inflammation in ADPKD patients. SEMA7A expression was lower after tolvaptan treatment, which may reflect drug efficacy.

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Title: Semaphorin 7A in circulating regulatory T cells is increased in autosomal-dominant polycystic kidney disease and decreases with tolvaptan treatment
Authors: Yashang Lee
Katrina Lehmann Blount
Feng Dai
Siobhan Thompson
Jonathan Kaufman Scher
Sherrie Bitterman
Madeline Droher
Erica L. Herzog
Gilbert Moeckel
Anil Karihaloo
Neera K. Dahl
Publication date: 01-08-2018
Publisher: Springer Singapore
Published in: Clinical and Experimental Nephrology / Issue 4/2018
Print ISSN: 1342-1751
Electronic ISSN: 1437-7799
DOI: https://doi.org/10.1007/s10157-018-1542-x

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Semaphorin 7A in circulating regulatory T cells is increased in autosomal-dominant polycystic kidney disease and decreases with tolvaptan treatment

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Background

Methods

Results

Conclusions

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