T cell subtypes and its therapeutic potential in autoimmune diseases and cancer

T cell subsets are the type of white blood cells tailoring specific immunity against different infections, the transformed cells, and perform an essential role in maintaining immune homeostasis. Based on the microenvironment and the cytokine milieu, the naive T cell differentiates to particular T cell subtypes and matures for specialized function to promote shaping of adaptive immunity. The crosstalk among different T cell subtypes regulates an array of immune responses such as antigen-specific B cell responses in terms of antibody production, inflammatory or anti-inflammatory cytokine production, immune tolerance, and development of adequate mucosal immunity. Dysregulation of T cell subtypes may disrupt the cytokine production and affect the functional integrity of the immune system, causing susceptibility to various infections, oncogenesis, low responses to vaccines, and autoimmune or chronic inflammatory diseases. This special issue of International Reviews of Immunology focuses on T cell biology, the complex communication among T cell subtypes in autoimmune disease, and the potential of T cell subtypes as an anti-cancer cell therapy through manipulated or unmanipulated T cell subsets via adoptive cell therapy (Figure 1).

Figure 1. T cell subtypes-associated with autoimmune disease, cancer and cancer immunotherapy.

The T cell subset known as regulatory T (Tregs) cells is well established in maintaining immune homeostasis and tolerance. There is an immense interest among scientists to explore the therapeutic potential of Tregs cells and translate it from bench to bedside. The first review article by Sharma and Rudra provides a comprehensive view of clinical strategies to modulate Treg cells functions, with an emphasis on various clinical studies establishing modulation of Treg cells as a valid clinical approach [1]. Under Tregs-based cell therapy, strides have been made in ex vivo expansion of autologous Tregs for adoptive Treg cell therapy. After the very successful application of chimeric antigen receptor (CAR) bearing T cells for therapy of certain lymphomas, efforts have been made to generate CAR-Tregs with specific antigen recognition. The article is beneficial to the broad reader and researchers doing basic research in T cells immunology, particularly researchers in academia and at pharmaceutical companies involved in cell immunotherapy (Figure 1).

Th9 cells (T helper cells predominantly producing IL-9) play an essential role in the elimination of extracellular pathogens and induce allergic responses along with mast cells in asthma. The emerging role of Th9 cells in inducing antitumor immune responses introduces new possibilities for cancer immunotherapy. Moreover, understanding the molecular pathways of Th9 cells differentiation also provides an opportunity to target pathways that are crucial for the upregulation of Th9 cells to treat cancer. In the second review article, Chandwaskar and Awasthi extensively summarize recent advancements in the biology of Th9 cells and possible implications in antitumor therapy and allergic inflammation [2]. This article also paves the way for cell-based immunotherapy for various cancer types (Figure 1).

Rheumatoid Arthritis (RA) is an autoimmune condition of the joints caused by the infiltration of inflammatory T cells, primarily Th17 cells. The review article by Vyas et al. summarizes the complex interplay of T helper subsets in RA [3]. While mortality is usually not associated with RA patients, quality of life is compromised in these individuals. This review highlights the latest classification of RA and discusses the role of Th1, Th2, Th17, Treg, and Th9 cells and their signature cytokines in the pathophysiology of the disease based on the latest scientific research work in the field. The balanced T helper cell responses are important in maintaining homeostatic conditions. However, in RA, Th1/Th2, and Th17/Treg balance is dysregulated and has been clarified in this review. Jak/STAT signaling, which is crucial in T helper cell differentiation, is also mentioned in the context of RA, and the authors discuss the therapeutic potential of Jak inhibitors for the treatment of RA. This article will be useful to immunologists, rheumatologists, and clinicians (Figure 1).

Post-transcriptional regulation is important for the fine-tuning of protein expression and its subsequent function. Non-coding RNA is the post-transcriptional regulator and broadly consist of three members: the long non-coding (lnc) RNA, the circular (cir) RNA, and the micro (mi) RNA. These regulatory RNAs are pivotal in the development and differentiation process of various biological process, including the development of specific T cell types. The last review by Roy et al describes the role of lncRNA and miRNA in T cell subset differentiation and sheds light on its dysregulation leading to the development of the autoimmune disease [4]. The authors also highlighted the potential of miRNA as a biomarker, which could be developed as a potential diagnostic and prognostic markers for various autoimmune diseases (Figure 1).