miR-155 promotes T follicular helper cell accumulation during chronic, low-grade inflammation.

Details

• Alternative Title:
  Immunity
• Personal Author:
  Hu, Ruozhen ; Kagele, Dominique A ; Huffaker, Thomas B ; Runtsch, Marah C ; Alexander, Margaret ; Liu, Jin ; Bake, Erin ; Su, Wei ; Williams, Matthew A ; Rao, Dinesh S ; Möller, Thomas ; Garden, Gwenn A. ; Round, June L ; O’Connell, Ryan M.
• Description:
  Chronic inflammation is a contributing factor to most life-shortening human diseases. However, the molecular and cellular mechanisms that sustain chronic inflammatory responses remain poorly understood, making it difficult to treat this deleterious condition. Using a mouse model of age-dependent inflammation that results from a deficiency in miR-146a, we demonstrate that miR-155 contributed to the progressive inflammatory disease that emerged as Mir146a(-/-) mice grew older. Upon analyzing lymphocytes from inflamed versus healthy middle-aged mice, we found elevated numbers of T follicular helper (Tfh) cells, germinal center (GC) B cells, and autoantibodies, all occurring in a miR-155-dependent manner. Further, Cd4-cre Mir155(fl/fl) mice were generated and demonstrated that miR-155 functions in T cells, in addition to its established role in B cells, to promote humoral immunity in a variety of contexts. Taken together, our study discovers that miR-146a and miR-155 counterregulate Tfh cell development that drives aberrant GC reactions during chronic inflammation.
• Subjects:
  Adoptive Transfer Animals Antigens, CD4 Article Autoantibodies B-Lymphocytes Cell Differentiation Disease Models, Animal Fos-Related Antigen-2 Germinal Center Immunity, Humoral Inflammation Lymphocyte Activation Mice Mice, Inbred C57BL Mice, Knockout MicroRNAs RNA, Small Interfering RNA Interference T-Lymphocytes, Helper-Inducer

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• Source:
  Immunity. 41(4):605-619.
• Pubmed ID:
  25367574
• Pubmed Central ID:
  PMC4657560
• Document Type:
  Journal Article
• Funding:
  5T32DK007115-39/DK/NIDDK NIH HHS/United States ; AI107090/AI/NIAID NIH HHS/United States ; DP2 GM111099/GM/NIGMS NIH HHS/United States ; DP2GM111099-01/DP/NCCDPHP CDC HHS/United States ; K08 CA133521/CA/NCI NIH HHS/United States ; K22 AI95375/AI/NIAID NIH HHS/United States ; R00 HL102228/HL/NHLBI NIH HHS/United States ; R00HL102228-05/HL/NHLBI NIH HHS/United States ; R01 CA166450/CA/NCI NIH HHS/United States ; R01CA166450-02/CA/NCI NIH HHS/United States ; R03NS070141/NS/NINDS NIH HHS/United States
• Volume:
  41
• Issue:
  4
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:4ea84b880ea7f9f87b714410f6fadca1074d4f8718d2d37f0b8e3e1f943dc649
• Download URL:
  https://stacks.cdc.gov/view/cdc/36219/cdc_36219_DS1.pdf
• File Type:
  [PDF - 3.28 MB ]