Marwa Chehimi1, Robert Ward2, Julien Pestel1, Maud Robert3, Sandra Pesenti1, Nadia Bendridi1, Marie-Caroline Michalski1, Martine Laville1,4, Hubert Vidal1, Assia Eljaafari1,5. 1. INSERM U 1060-CarMen, University Claude Bernard Lyon I, 165 Chemin du Grand Revoyet, 69310, Pierre Bénite, France. 2. Department of Nutrition, Dietetics, and Food Sciences, Utah State University, Old Main Hill, Logan, Utah, 84322, USA. 3. Department of Surgery in Gastro-enterology, Edouard Herriot Hospital, 1 place d'Arsonval, 69003, Lyon, France. 4. Department of Nutrition, South Lyon Hospital, Hospices Civils de Lyon, 165 Chemin du Grand Revoyet, 69310, Pierre Bénite, France. 5. Research DO-IT Team, Hospices Civils de Lyon, Faculte de Medecine Lyon Sud, Inserm U1060-CarMen, 165 Chemin du Grand Revoyet, 69310, Pierre Bénite, France.
Abstract
SCOPE: Obese adipose tissue (AT) is infiltrated by inflammatory immune cells including IL-17A-producing-T (Th17) cells. It has been previously demonstrated that adipose-derived stem cells from obese (ob-ASCs), but not lean AT promote Th17 cells. Because n-3 PUFAs are known to inhibit obese AT inflammation, it is tested here whether they could inhibit ob-ASC-mediated IL-17A secretion. METHODS AND RESULTS: The n-3 PUFA precursor, alpha-linolenic acid (ALA), or its derivatives, eicosapentaenoic, or docosahexaenoic acid, is added to co-cultures of human ob-ASCs and mononuclear cells (MNCs). All three inhibited IL-17A, but not IL-1β, IL-6, nor TNFα secretion. As a control, palmitic acid (PA), a saturated fatty acid, did not inhibit IL-17A secretion. ALA also inhibited IL-17A secretion mediated by adipocytes differentiated from ob-ASCs. Toll-like-receptor 4 is shown to be involved in ob-ASC-mediated-IL-17A secretion, and to be inhibited by ALA, together with Cyclo-Oxygenase-2 and Signal-Transducer-and-Activator-of-transcription-3. In addition, ALA down-regulated Intercellular-Adhesion-Molecule-1 (ICAM-1) expression in both monocytes and ASCs, which resulted in decreased interactions between ob-ASCs and MNCs, and inhibition of IL-17A secretion. CONCLUSION: It is demonstrated herein that ALA inhibits Th17 cell promotion, through decreased ICAM-1expression in both ob-ASCs and monocytes. This novel mechanism may contribute to explain the beneficial effects of n-3 PUFA in IL-17A-related inflammatory pathologies.
SCOPE: n class="Disease">Obese adipose tissue (AT) is infiltrated by inflammatory immune cells including n>n class="Gene">IL-17A-producing-T (Th17) cells. It has been previously demonstrated that adipose-derived stem cells from obese (ob-ASCs), but not lean AT promote Th17 cells. Because n-3 PUFAs are known to inhibit obese AT inflammation, it is tested here whether they could inhibit ob-ASC-mediated IL-17A secretion. METHODS AND RESULTS: The n-3 PUFA precursor, alpha-linolenic acid (ALA), or its derivatives, eicosapentaenoic, or docosahexaenoic acid, is added to co-cultures of human ob-ASCs and mononuclear cells (MNCs). All three inhibited IL-17A, but not IL-1β, IL-6, nor TNFα secretion. As a control, palmitic acid (PA), a saturated fatty acid, did not inhibit IL-17A secretion. ALA also inhibited IL-17A secretion mediated by adipocytes differentiated from ob-ASCs. Toll-like-receptor 4 is shown to be involved in ob-ASC-mediated-IL-17A secretion, and to be inhibited by ALA, together with Cyclo-Oxygenase-2 and Signal-Transducer-and-Activator-of-transcription-3. In addition, ALA down-regulated Intercellular-Adhesion-Molecule-1 (ICAM-1) expression in both monocytes and ASCs, which resulted in decreased interactions between ob-ASCs and MNCs, and inhibition of IL-17A secretion. CONCLUSION: It is demonstrated herein that ALA inhibits Th17 cell promotion, through decreased ICAM-1expression in both ob-ASCs and monocytes. This novel mechanism may contribute to explain the beneficial effects of n-3 PUFA in IL-17A-related inflammatory pathologies.
Authors: Annette L West; Elizabeth A Miles; Lihua Han; Karen A Lillycrop; Johnathan A Napier; Philip C Calder; Graham C Burdge Journal: Nutrients Date: 2021-09-05 Impact factor: 5.717