Expansion of an osteopontin‐expressing T follicular helper cell subset correlates with autoimmunity in B6.Sle1b mice and is suppressed by the H1‐isoform of the Slamf6 receptor. Issue 8 (29th April 2013)
- Record Type:
- Journal Article
- Title:
- Expansion of an osteopontin‐expressing T follicular helper cell subset correlates with autoimmunity in B6.Sle1b mice and is suppressed by the H1‐isoform of the Slamf6 receptor. Issue 8 (29th April 2013)
- Main Title:
- Expansion of an osteopontin‐expressing T follicular helper cell subset correlates with autoimmunity in B6.Sle1b mice and is suppressed by the H1‐isoform of the Slamf6 receptor
- Authors:
- Keszei, Marton
Detre, Cynthia
Castro, Wilson
Magelky, Erica
O'Keeffe, Michael
Kis‐Toth, Katalin
Tsokos, George C.
Wang, Ninghai
Terhorst, Cox - Abstract:
- Abstract : The costimulatory receptor Slamf6 partially controls lupus‐related autoimmunity in congenic Sle1b mice; for instance, the presence of the protein isoform Slamf6‐H1 in Sle1b.Slamf6‐H1 mice mitigates disease. Here, we report that young Sle1b mice, but not Sle1b.Slamf6‐H1 or B6 mice, contain a memory T‐helper cell subset identified by ∗∗∗ [mt]2‐fold increase in expression of 17 genes, chief among which is Spp1, encoding the cytokine osteopontin (OPN). These T follicular helper (TFH ) cells, including OPN + T FH cells, expand concomitantly with severity of the disease. By contrast, Sle1b.Slamf6‐H1 or Sle1b.SAP – / – mice do not develop autoantibodies and the number of TFH cells is 5 times lower than in age‐matched Sle1b mice. By comparing Sle1b and Sle1b.OPN – / – mice, we find that the lack of OPN expression impedes early autoantibody production. Furthermore, on the adoptive transfer of Sle1b.OPN – / – CD4 + T cells into bm12 recipients autoantibody production and germinal center formation is reduced compared to recipients of Sle1b.OPN+/+ CD4 + T cells. We propose a model in which OPN provides a survival signal for a precursor TFH cell subset, which is a key factor in autoimmunity. Keszei, M., Detre, C., Castro, W., Magelky, E., O'Keeffe, M., Kis‐Toth, K., Tsokos, G. C., Wang, N., Terhorst, C. Expansion of an osteopontin‐expressing T follicular helper cell subset correlates with autoimmunity in B6.Sle1b mice and is suppressed by the H1‐isoform of the Slamf6 receptor.Abstract : The costimulatory receptor Slamf6 partially controls lupus‐related autoimmunity in congenic Sle1b mice; for instance, the presence of the protein isoform Slamf6‐H1 in Sle1b.Slamf6‐H1 mice mitigates disease. Here, we report that young Sle1b mice, but not Sle1b.Slamf6‐H1 or B6 mice, contain a memory T‐helper cell subset identified by ∗∗∗ [mt]2‐fold increase in expression of 17 genes, chief among which is Spp1, encoding the cytokine osteopontin (OPN). These T follicular helper (TFH ) cells, including OPN + T FH cells, expand concomitantly with severity of the disease. By contrast, Sle1b.Slamf6‐H1 or Sle1b.SAP – / – mice do not develop autoantibodies and the number of TFH cells is 5 times lower than in age‐matched Sle1b mice. By comparing Sle1b and Sle1b.OPN – / – mice, we find that the lack of OPN expression impedes early autoantibody production. Furthermore, on the adoptive transfer of Sle1b.OPN – / – CD4 + T cells into bm12 recipients autoantibody production and germinal center formation is reduced compared to recipients of Sle1b.OPN+/+ CD4 + T cells. We propose a model in which OPN provides a survival signal for a precursor TFH cell subset, which is a key factor in autoimmunity. Keszei, M., Detre, C., Castro, W., Magelky, E., O'Keeffe, M., Kis‐Toth, K., Tsokos, G. C., Wang, N., Terhorst, C. Expansion of an osteopontin‐expressing T follicular helper cell subset correlates with autoimmunity in B6.Sle1b mice and is suppressed by the H1‐isoform of the Slamf6 receptor. FASEB J. 27, 3123–3131 (2013). www.fasebj.org … (more)
- Is Part Of:
- FASEB journal. Volume 27:Issue 8(2013)
- Journal:
- FASEB journal
- Issue:
- Volume 27:Issue 8(2013)
- Issue Display:
- Volume 27, Issue 8 (2013)
- Year:
- 2013
- Volume:
- 27
- Issue:
- 8
- Issue Sort Value:
- 2013-0027-0008-0000
- Page Start:
- 3123
- Page End:
- 3131
- Publication Date:
- 2013-04-29
- Subjects:
- Ly108 -- SAP -- systemic lupus erythematosus -- OPN -- TFH
Biology -- Periodicals
Biology, Experimental -- Periodicals
570 - Journal URLs:
- http://onlinelibrary.wiley.com/ ↗
- DOI:
- 10.1096/fj.12-226951 ↗
- Languages:
- English
- ISSNs:
- 0892-6638
- Deposit Type:
- Legaldeposit
- View Content:
- Available online (eLD content is only available in our Reading Rooms) ↗
- Physical Locations:
- British Library DSC - BLDSS-3PM
British Library HMNTS - ELD Digital store - Ingest File:
- 13222.xml