| First Author | Kim V | Year | 2022 |
| Journal | JCI Insight | Volume | 7 |
| Issue | 11 | PubMed ID | 35674135 |
| Mgi Jnum | J:326447 | Mgi Id | MGI:7294907 |
| Doi | 10.1172/jci.insight.157332 | Citation | Kim V, et al. (2022) IL-17-producing follicular Th cells enhance plasma cell differentiation in lupus-prone mice. JCI Insight 7(11):e157332 |
| abstractText | Follicular Th (Tfh) cells are key CD4+ Th cells involved in regulating B cell differentiation in the germinal center. Mice with conditional KO (CKO) of B lymphocyte-induced maturation protein-1 (BLIMP-1) expression in CD11chi DCs (Prdm1 CKO) spontaneously develop a lupus-like disease. We found an increase in the number of Tfh cells in secondary lymphoid organs in lupus-prone Prdm1-CKO mice. B cells stimulated with Tfh cells become Ab-secreting cells (ASCs); there was an increase in ASC differentiation mediated by Tfh cells from Prdm1-CKO mice compared with Tfh cells from control mice. This was mainly due to the increased expression of molecules within the IL-23/IL-17 pathway in Tfh cells from Prdm1-CKO mice. There was an increased frequency of IL-17A+ Tfh cells in Prdm1-CKO mice. These Tfh cells secrete IL-17A and an increased amount of IL-21. Furthermore, neutralizing IL-17A and IL-21 reduced ASC differentiation induced by Tfh cells. Lastly, we found the expression of IL-1beta and IL-6 was increased in BLIMP-1-deficient DCs, which are key for Th17 induction. Altogether, the lack of BLIMP-1 expression in DCs induces not only an increased number of Tfh cells, but also functionally distinct Tfh cells that lead to increased ASC differentiation. |
