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We previously demonstrated reduced levels of circulating IL-7 in rheumatoid arthritis (RA), although high amounts are expressed in joints, suggesting differences between systemic and synovial effects. We observed healthy levels of IL-7 in 48% of RA patients in clinical remission (CR) and aimed to investigate the consequences of IL-7 deficiency on T-cell responses.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>We used RA patients with active disease and in CR presenting various levels of IL-7, to investigate its modulatory effects on T cells by analysing responses to phyto-haemagglutinin (PHA), expression of polarization or survival factors, or suppression by regulatory T cells (Tregs).<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>IL-7 levels were normal (&gt;10\u00a0pg\/ml) in 48% of RA patients in CR. Amongst 63 CR patients followed up for 18\u00a0months, lack of IL-7 recovery was observed in 13 out of 15 (86%) patients experiencing relapse but only 11 out of 48 (23%) of those who did not (<jats:italic>P<\/jats:italic>\u2009=\u20090.0002). Binary regressions showed high significance for below normal IL-7 levels for self-reported maternal family history of arthritis (odds ratio (OR): 7.66, <jats:italic>P<\/jats:italic>\u2009=\u20090.006) and a trend for smoking (OR: 3.33, <jats:italic>P<\/jats:italic>\u2009=\u20090.068) with no further demographic or clinical associations. Serum IL-7 correlated with restored CD4<jats:sup>+<\/jats:sup>T-cell response to PHA (rho\u2009=\u20090.879); this was not related to an increase in T-cell proliferation capacity or expression of survival factors B-cell lymphoma 2 (BCL2) and BCL2-associated protein X (BAX). Expression of Th1 polarization factor (<jats:italic>TBET<\/jats:italic>) was also dependent on exposure to IL-7 <jats:italic>in vivo<\/jats:italic> (rho\u2009=\u20090.600). In contrast CD25<jats:sup>high<\/jats:sup>Tregs\u2019 response to PHA was not affected by <jats:italic>in vivo<\/jats:italic> IL-7, but their suppression capabilities were related to circulating IL-7 (rho\u2009=\u20090.589). Co-stimulation with IL-7 (mimicking the joint environment) increased responsiveness of CD4<jats:sup>+<\/jats:sup>T-cells to PHA, lowering the ability of CD25<jats:sup>high<\/jats:sup>Tregs to suppress them.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>Our data demonstrate that IL-7 has a critical role in modulating T-cell function <jats:italic>in vivo,<\/jats:italic> possibly explaining opposing effects observed systemically and in the joint. Lack of IL-7 recovery in CR by maintaining a suppressed immune system may be a determinant factor in the occurrence of relapse.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/s13075-014-0511-3","type":"journal-article","created":{"date-parts":[[2014,12,22]],"date-time":"2014-12-22T11:50:44Z","timestamp":1419249044000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Modulation of peripheral T-cell function by interleukin-7 in rheumatoid arthritis"],"prefix":"10.1186","volume":"16","author":[{"given":"Sarah M","family":"Churchman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jehan J","family":"El-Jawhari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata N","family":"Burska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rekha","family":"Parmar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Go\u00ebb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip G","family":"Conaghan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Emery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederique","family":"Ponchel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,12,23]]},"reference":[{"key":"511_CR1","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1016\/S0065-2776(08)60456-3","volume":"56","author":"R Winchester","year":"1994","unstructured":"Winchester R: The molecular basis of susceptibility to rheumatoid arthritis. 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