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TLR3 Activation Preferentially Enhances IL‐17F Expression in SHR Immune Cells
Author(s) -
Singh Madhu,
Cicha Michael,
Chapleau Mark,
Abboud François
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.667.2
Subject(s) - medicine , endocrinology , splenocyte , immune system , flow cytometry , inflammation , interleukin 17 , t cell , ionomycin , chemistry , immunology , calcium
We have shown abnormally large age‐related increases in CD161+ immune cell populations in splenocytes from spontaneously hypertensive rats (SHR). A subpopulation of CD161+ cells (Th17, CD4+CD161+) expresses IL‐17A and IL‐17F. IL‐17A plays a key role in hypertension and related vascular injury. However, structurally and functionally similar IL‐17F has not been studied in hypertension. Using flow cytometry, we found a greater abundance of CD4+CD161+ cells in prehypertensive SHR splenocytes than in normotensive Wistar‐Kyoto rats (WKY). These cells increased with age reaching levels of 14.7 ± 0.1% in spleens from 38 week old SHR compared to 8.5 ± 0.6% in age matched WKY. While PMA‐ionomycin caused equivalent induction of TNF‐α (WKY 6.7 fold, SHR 6.7 fold) and IL‐17A RNA (WKY 14.3 fold, SHR 12.4 fold), the induction of IL‐17F RNA was significantly greater in SHR splenocytes (WKY 46.3 fold, SHR 65.2 fold). When challenged with poly‐IC, a TLR3 agonist, TNF‐α and IL‐17A expressions were modestly increased in SHR, however, expression of IL‐17F was markedly and specifically increased in SHR compared to WKY (27 fold SHR vs. 3 fold in WKY). We conclude that (1) SHR splenocytes have significantly greater potential for IL‐17F induction under inflammatory conditions, and (2) increased expression of IL‐17F is much more pronounced than that of IL‐17A in response to TLR3 activation in SHR. IL‐17F may be a novel and preferred therapeutic target in hypertension. Funded by NIH PPG HL14388.