Novel Peripheral Helper T Cells in RA Save

Nature has published the findings from a group of US and UK researchers who have identified a unique subset of helper T-cells called ‘peripheral helper’ T-cells, or Tph cells, that are found in the synoviums and may be linked to the pathogenesis of rheumatoid arthritis (RA).

Using use mass cytometry to analyse activated T cells in the synovial tissue of RA patients, they identified a markedly expanded population of PD-1^hiCXCR5^-CD4⁺ T cells. According to cytometry, transcriptomics, and functional assays, this populatoin of peripheral helper T (T_PH) cells express factors enabling B-cell help, including IL-21, CXCL13, ICOS, and MAF.

Like T follicular helper cells, T_PH cells induce plasma cell differentiation.  The difference between T_PH cells and T follicular helper cells includes the altered expression of BCL6 and BLIMP1 and the expression of chemokine receptors (CCR2, CX3CR1, CCR5) that direct migration to inflamed sites. T_PH cells appear to be uniquely poised to promote B-cell responses and antibody production within pathologically inflamed non-lymphoid tissues.

Thus Tph cells, are similar to the follicular helper T-cells  in that they can induce B-cell differentiation, but Tph cells are genetically distinct in that they are able to migrate to RA-affected joint tissue, where they can interact with B-cells locally and attract other inflammatory cells.

The authors propose a pivotal role for these cells suggesting they may be a potential target for future therapy in the treatment of RA.