Regulatory T cells manifest IFN-α mediated protection during antigen induced arthritis

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Chalise, Jaya PrakashLinköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten (author)

Regulatory T cells manifest IFN-α mediated protection during antigen induced arthritis

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LIBRIS-ID:oai:DiVA.org:liu-122462
https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-122462URI

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Language:English
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IntroductionType I interferon induces tolerance against arthritogenic antigen and protects against antigen induced arthritis (AIA). Regulatory T cells (Treg cells) resolve aberrant immune reaction, maintain self-tolerance and prevent the development of autoimmune diseases. We here investigated the impact of Interferon alpha (IFN-α) on Treg cells development and function during antigen induced arthritis.MethodsFor AIA, mice were immunized with methylated bovine serum albumin (mBSA) at day 1 and 7 in presence or absence of IFN-α. At day 21, arthritis was induced by intra-articular injection of mBSA and arthritis was evaluated at day 28. At various days of AIA, CD4, CD25, Foxp3 and CTLA-4 expression was quantified by FACS in blood cells, splenocytes, lymph nodes cells and in ex vivo re-stimulated leucocytes (pooled splenocytes and lymph nodes cells) isolated at same days. To investigate the importance of Treg cells in IFN-α protection in AIA, Foxp3DTReGFP+mice were used, where Treg cells can be depleted transiently by administration of diptherin toxin. CFSE based suppression assay was used to assess the suppression by Treg cells isolated day 4, 10, 20 of AIA against proliferation of mBSA or anti-CD3 stimulated responder T cells (Tresp cells) isolated at same days. For adoptive transfer experiments, 250,000 Treg cells from IFN-α treated or untreated mice day 20 of AIA were intravenously injected to recipient pre-immunized mice without IFN-α treatment during the induction of arthritis. The importance of IFN-α signalling on T cells for the IFN-α protection was evaluated by using CD4-Cre+/- IFNAR flox/flox mice.ResultsProtective effects of IFN-α in AIA were associated with significant TGF-β dependent increase in Foxp3+ T cells in blood at day 4 and minor increase of Foxp3+T cells in spleen and lymph node cells. However IFN-α signalling in T cells is not required for IFN-α-protection. Upon ex vivo re-stimulation in presence of IFN-α with mBSA but not anti-CD3, the Treg cells numbers were increased in leucocytes isolated from day 4 and day 10 of AIA. Transient depletion of Treg cells during induction of arthritis (day 21) abolished IFN-α-protection however the protection was not affected when Treg cells are depleted during immunization phase (day 1 and day 7). Against mBSA-stimulated proliferation of Tresp cells, suppression by Treg cells isolated from day 10 and day 20 from IFN-α treated mice are significantly higher than Treg cells from untreated mice. Treg cells isolated from IFN-α or untreated mice at day 20 of AIA when transferred to pre-immunized untreated mice prevent the development of arthritis.ConclusionTreg cells are critically associated with IFN-α protective effects in AIA. IFN-α enhances TGF-β dependent early development of Treg cells and later IFN-α enhances their suppressive capacity against T cells proliferation in antigen specific manner during AIA.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Farmakologi och toxikologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Pharmacology and Toxicology hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Reumatologi och inflammation hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Rheumatology and Autoimmunity hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine hsv//eng
Interferon alpha
regulatory T cells
antigen induced arthritis
TGF-beta

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Chenna Narendra, SudeepLinköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten(Swepub:liu)sudch29 (author)
Biggs, SophieRegion Östergötland, Reumatologiska kliniken i Östergötland (author)
Kalinke, UlrichTwincore, Germany(Swepub:liu)bjoca98 (author)
Iacono, AlbertaDepartment of Experimental Medicine, University of Perugia, Perugia, Italy (author)
Boon, LouisEPIRUS Biopharmaceuticals, Utrecht, Netherlands (author)
Magnusson, MattiasLinköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten(Swepub:liu)matma88 (author)
Linköpings universitetAvdelningen för neuro- och inflammationsvetenskap (creator_code:org_t)

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Pharmacology and ...

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