PMID- 27029527
OWN - NLM
STAT- MEDLINE
DCOM- 20170213
LR  - 20181113
IS  - 1476-5470 (Electronic)
IS  - 1466-4879 (Print)
IS  - 1466-4879 (Linking)
VI  - 17
IP  - 4
DP  - 2016 Jun
TI  - The autoimmunity-associated gene RGS1 affects the frequency of T follicular 
      helper cells.
PG  - 228-38
LID - 10.1038/gene.2016.16 [doi]
AB  - RGS1 (regulator of G-protein signaling 1) has been associated with multiple 
      autoimmune disorders including type I diabetes. RGS1 desensitizes the chemokine 
      receptors CCR7 and CXCR4 that are critical to the localization of T and B cells 
      in lymphoid organs. To explore how RGS1 variation contributes to autoimmunity, we 
      generated Rgs1 knockdown (KD) mice in the nonobese diabetic (NOD) model for type 
      I diabetes. We found that Rgs1 KD increased the size of germinal centers, but 
      decreased the frequency of T follicular helper (TFH) cells. We show that loss of 
      Rgs1 in T cells had both a T cell-intrinsic effect on migration and TFH cell 
      frequency, and an indirect effect on B-cell migration and germinal center 
      formation. Notably, several recent publications described an increase in 
      circulating TFH cells in patients with type I diabetes, suggesting this cell 
      population is involved in pathogenesis. Though Rgs1 KD was insufficient to alter 
      diabetes frequency in the NOD model, our findings raise the possibility that RGS1 
      plays a role in autoimmunity owing to its function in TFH cells. This mechanistic 
      link, although speculative at this time, would lend support to the notion that 
      TFH cells are key participants in autoimmunity and could explain the association 
      of RGS1 with several immune-mediated diseases.
FAU - Caballero-Franco, C
AU  - Caballero-Franco C
AD  - Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.
FAU - Kissler, S
AU  - Kissler S
AD  - Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.
LA  - eng
GR  - P30 DK036836/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20160331
PL  - England
TA  - Genes Immun
JT  - Genes and immunity
JID - 100953417
RN  - 0 (RGS Proteins)
RN  - 0 (Rgs1 protein, mouse)
SB  - IM
MH  - Animals
MH  - Autoimmunity/genetics
MH  - Diabetes Mellitus, Type 1/*genetics/immunology
MH  - Germinal Center/*pathology
MH  - HEK293 Cells
MH  - Humans
MH  - Mice
MH  - Mice, Inbred NOD
MH  - RGS Proteins/*genetics/metabolism
MH  - T-Lymphocytes, Helper-Inducer/*pathology
PMC - PMC4892947
MID - NIHMS763948
COIS- CONFLICT OF INTEREST DISCLOSURE The authors declare no conflict of interest.
EDAT- 2016/04/01 06:00
MHDA- 2017/02/14 06:00
PMCR- 2016/09/30
CRDT- 2016/04/01 06:00
PHST- 2016/01/07 00:00 [received]
PHST- 2016/02/19 00:00 [revised]
PHST- 2016/02/25 00:00 [accepted]
PHST- 2016/04/01 06:00 [entrez]
PHST- 2016/04/01 06:00 [pubmed]
PHST- 2017/02/14 06:00 [medline]
PHST- 2016/09/30 00:00 [pmc-release]
AID - gene201616 [pii]
AID - 10.1038/gene.2016.16 [doi]
PST - ppublish
SO  - Genes Immun. 2016 Jun;17(4):228-38. doi: 10.1038/gene.2016.16. Epub 2016 Mar 31.