University of Chicago, USA
Haochu Huang has completed his Ph.D. from Johns Hopkins University and postdoctoral studies in the lab of Drs. Christophe Benoist and Diane Mathis at Harvard Medical School. His work focuses on tolerance and regulation of autoreactive T cells and B cells in normal immune system and autoimmune diseases.
Cytokines are major regulators of immune responses. Particularly, IL-21 is a pluripotent cytokine that regulates B cell and plasma cell diff erentiation, and is thought to be an autocrine factor for TFH and TH17 diff erentiation, two T cell subsets implicated in autoimmunity. Th e relevant cellular source and target cells of IL-21 in autoimmunity have not been well characterized. We investigated this issue in the K/BxN mice by comparing the ability to induce arthritis of wildtype KRN T cells, IL-21 knockout KRN T cells that cannot produce IL-21, IL-21 receptor knockout KRN T cells or B cells that cannot signal by IL-21, or RORt knockout KRN T cells that are defective in Th 17 diff erentiation. Our results showed that IL-21 production by TFH but not TH17 T cells is critical for arthritis development. However, IL-21 does not act on T cells as an autocrine factor but rather acts on B cells to form germinal centers and produce autoantibodies. Th ese results clarify the roles of IL-21 signaling to T cells or B cells in autoimmune diseases and have implications in developing eff ective therapies for rheumatoid arthritis and other antibody-mediated autoimmune diseases.