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The molecular mechanisms of these beneficial effects are only partially understood. <jats:styled-content style=\"fixed-case\">DHA<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">EPA<\/jats:styled-content> activate <jats:italic>Free Fatty Acid receptor 4<\/jats:italic> (<jats:styled-content style=\"fixed-case\">GPR<\/jats:styled-content>120\/<jats:styled-content style=\"fixed-case\">FFA<\/jats:styled-content>4). Recently, the first orally available, synthetic ligand of <jats:styled-content style=\"fixed-case\">FFA<\/jats:styled-content>4, 3\u2010[2\u2010chloro\u20105\u2010(trifluoromethoxy)phenyl]\u20103\u2010azaspiro[5.5]undecane\u20109\u2010acetic acid (\u201ccompound A\u201d; cpd A) has been developed. Cpd A exhibits distinctly higher potency, efficiency, and selectivity at <jats:styled-content style=\"fixed-case\">FFA<\/jats:styled-content>4 than \u03c93\u2010<jats:styled-content style=\"fixed-case\">PUFA<\/jats:styled-content>s and ameliorates insulin resistance and adipose tissue inflammation in the mouse. With <jats:styled-content style=\"fixed-case\">GPR<\/jats:styled-content>120\/<jats:styled-content style=\"fixed-case\">FFA<\/jats:styled-content>4 activation believed to also attenuate tissue inflammation in autoimmune diseases, cpd A may also have a beneficial effect in these diseases. We have therefore addressed the therapeutic potential of cpd A in mouse models of three prototypical autoimmune diseases, specifically psoriasis, rheumatoid arthritis, and bullous pemphigoid. The effect of cpd A on the course of Aldara\u2122\u2010induced psoriasis\u2010like dermatitis, K\/BxN serum transfer arthritis, and antibody transfer pemphigoid disease\u2010like dermatitis was scrutinized. Cpd A did not alter the course of Aldara\u2010induced psoriasis\u2010like dermatitis, K\/BxN serum transfer arthritis, or antibody transfer pemphigoid disease\u2010like dermatitis. Our results suggest that therapeutic regimens solely relying on <jats:styled-content style=\"fixed-case\">FFA<\/jats:styled-content>4 activation do not bear the potential to treat inflammatory diseases. With cpd A distinctly more potent in activating <jats:styled-content style=\"fixed-case\">GPR<\/jats:styled-content>120\/<jats:styled-content style=\"fixed-case\">FFA<\/jats:styled-content>4 than \u03c93\u2010<jats:styled-content style=\"fixed-case\">PUFA<\/jats:styled-content>s, this also suggests that <jats:styled-content style=\"fixed-case\">GPR<\/jats:styled-content>120\/<jats:styled-content style=\"fixed-case\">FFA<\/jats:styled-content>4 activation by \u03c93\u2010<jats:styled-content style=\"fixed-case\">PUFA<\/jats:styled-content>s does not significantly contribute to the health\u2010promoting effects of \u03c93\u2010<jats:styled-content style=\"fixed-case\">PUFA<\/jats:styled-content>s in autoimmune diseases.<\/jats:p>","DOI":"10.1002\/prp2.438","type":"journal-article","created":{"date-parts":[[2018,11,8]],"date-time":"2018-11-08T15:14:40Z","timestamp":1541690080000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Oral administration of the selective <scp>GPR<\/scp>120\/<scp>FFA<\/scp>4 agonist compound A is not effective in alleviating tissue inflammation in mouse models of prototypical autoimmune diseases"],"prefix":"10.1002","volume":"6","author":[{"given":"Melanie","family":"Wannick","sequence":"first","affiliation":[{"name":"Department of Dermatology, Allergy, and Venereology University of L\u00fcbeck L\u00fcbeck Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siegfried","family":"Bezdek","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Allergy, and Venereology University of L\u00fcbeck L\u00fcbeck 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