{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:08:02Z","timestamp":1787836082512,"version":"build-2784847793"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T00:00:00Z","timestamp":1626393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The K\/BxN mouse model of rheumatoid arthritis (RA) closely resembles the human disease. In this model, arthritis results from activation of autoreactive KRN T cells recognizing the glycolytic enzyme glucose-6-phosphate isomerase (GPI) autoantigen, which provides help to GPI-specific B cells, resulting in the production of pathogenic anti-GPI antibodies that ultimately leads to arthritis symptoms from 4 weeks of age. Vasoactive intestinal peptide (VIP) is a neuropeptide broadly distributed in the central and peripheral nervous system that is also expressed in lymphocytes and other immune cell types. VIP is a modulator of innate and adaptive immunity, showing anti-inflammatory and immunoregulatory properties. Basically, this neuropeptide promotes a shift in the Th1\/Th2 balance and enhances dedifferentiation of T regulatory cells (Treg). It has demonstrated its therapeutic effects on the collagen-induced arthritis (CIA) mouse model of RA. In the present hypothesis and theory article, we propose that the immunoregulatory properties of VIP may be due likely to the inhibition of T cell plasticity toward non-classic Th1 cells and an enhanced follicular regulatory T cells (Tfr) activity. The consequences of these regulatory properties are the reduction of systemic pathogenic antibody titers.<\/jats:p>","DOI":"10.3389\/fimmu.2021.701862","type":"journal-article","created":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T11:32:33Z","timestamp":1626435153000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Mechanism of Immunoregulatory Properties of Vasoactive Intestinal Peptide in the K\/BxN Mice Model of Autoimmune Arthritis"],"prefix":"10.3389","volume":"12","author":[{"given":"Javier","family":"Leceta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina 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