Ulcerative colitis is characterised by a plasmablast-skewed humoral response

Uzzan M, Martin J, Mesin L, et al. Ulcerative colitis is characterised by a plasmablast-skewed humoral response associated with disease activity. Nat Med 2022; doi: 10.1038/s41591-022-01680-y

In healthy individuals, the intestinal B cell responses act to try and maintain homeostasis by generation of IgA-producing plasma cells, which help promote tolerance on mucosal surfaces. Plasma cells can also produce IgG and it has been demonstrated that these may play a role in gut inflammation. This study used single cell RNA sequencing, single cell IgG gene sequencing and protein level validation to map the compositional, transcriptional and the landscape of colonic mucosal circulating B cells in patients with ulcerative colitis (UC).

Patients with UC had an expansion of naïve B cells and IgG +plasma cells with curtailed diversity and maturation. They suggested that this IgG enriched B cell response could be responsible for the amplification of local inflammatory cascades driven by Fcγ receptors-dependent recruitment of inflammatory monocytes and TH₁₇ (T helper 17) cells. Furthermore, β7+ (beta 7 positive) plasmablasts/plasma cells in blood correlated with UC activity.

This dysregulated response was tracked back to activated/effector T cells expressing levels of effector cytokines. Furthermore, they noted that inflammatory macrophages showed expression of CXCL9 (chemokine ligand 9), which is a chemokine, expressed by inflammatory macrophages, which may contribute to this dysregulation of B cells. Importantly, intestinal CXCL13 (chemokine ligand 13)-expressing T follicular helper-like cells were associated with this pathogenic B cell response overall suggesting that a type 1 immunity is likely to contribute to these B cell responses, culminating towards an IgG production in the intestine of patients with UC.

Spatiotemporal differences in production and effects of interleukin 22 in gut immunity

Zindl C, Witte S, Laufer V, et al. A non-redundant role for T cell-derived interleukin 22 in antibacterial defence of colonic crypts Immunity 2022; doi: 10.1016/j.immuni.2022.02.003.

Interleukin 22 (IL-22) plays a key …