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This is an expansion of the Lymphotoxin alpha article.

Role of Lymphotoxin alpha in autoimmunity
Lymphotoxin alpha based therapies offer a new and effective approach to treating autoimmune diseases, in ways that have not been previously possible. LT alpha is a very promising protein because of its elevated presence in pathogenic immune cells. By creating drugs that affect LT alpha and its receptor LTbR-Ig (lymphotoxin beta receptor), scientists are able to offer an effective alternative to current autoimmune therapies that destroy the patient’s immune system, which severely diminishes their quality of life and can expose them to potentially lethal infections. Another reason why LT alpha and LTbR-Ig based therapies could potentially groundbreaking is their versatility and effectiveness in more than one single autoimmune disease, which will be discussed in more detail below. Lymphotoxin alpha plays critical role in the maintenance of the lymphoid microenvironment architecture, as well as in the development of the lymph nodes. The lymphoid microenvironment is responsible for the transport and organization of chemical signals, proteins, and other components of the immune response. By changing the structure of this environment, through the inhibition of LT alpha, the autoimmune response of a cell can be manipulated. While the effects of altering this microenvironment have not been greatly explored, inhibition of the LT alpha pathway has been shown to inhibit some effects of many autoimmune disease models. 

Surface LT present on pathogenic T cell populations
The uncontrolled proliferation of helper T cells (TH Cells) plays a significant part in certain autoimmune responses. However, trying to kill helper T cells in general would prove deleterious since only certain types of TH cells have been associated with autoimmune responses, specifically TH1 and TH17 cells. Surface LT, specifically the heterotrimer form LTa1b2 has been found on these pathogenic T cell populations, and therefore new therapies are being developed that target LT alpha on these destructive T cells to combat autoimmunity. This therapeutic approach is highly selective; meaning the healthy T cells that protect the host body from infection, are not affected. Keeping these healthy cells alive helps minimize the side effects associated with other types of therapies that deplete both healthy and non-healthy T-cells. These side effects can result in dangerous infections, such as tuberculosis, since an important part of the immune response has just been destroyed. Depleting these T cell populations is advantageous because once they have been destroyed; the new helper T cells that are created to replace them no longer have autoimmune characteristics. The potential to permanently eliminate autoimmune T cells could result in the patient being cured.

Soluble LT alpha in Graft versus Host disease
Graft-versus-host Disease (GVHD) is a complication of bone marrow transplantation procedures during which immune cells from the grafted tissue mount an immune response against the host cells. This response can result in significant damage to the hosts internal organs and tissues, specifically skin, liver and gastrointestinal tract tissues, and it is often lethal. GVHD is induced by effector T cells and inflammatory cytokines, which cause increased damage to host tissues due to the pretransplantation chemotherapy and radiotherapy.

Studies have been shown that LT-αlpha plays a significant role in graft versus host disease, since donor T cells are capable of secreting the soluble homotrimeric molecule LT alpha-3 after transplantation, which causes an inflammatory immune response in the recipient, which develops into GVHD. These studies have also shown that by blocking the secretion of LT alpha-3 in the donor T cells protected the recipients from developing GVHD, while preserving the T cells functionality. This is significant because the complications that are associated with GVHD can be avoided, without the patient becoming immunocompromised. Another interesting aspect of LT alpha role in GVHD is that only the homotrimer LTα3 is involved in the pathogenicity of GVHD, not the heterotrimer LTα1β2, which is a surface antigen instead of a soluble molecule. The reason why only LT alpha-3 is involved in GVHD pathogenicity remains unknown.

Anti LT alpha antibodies
Anti LT alpha antibodies are one of the newest and most promising therapies in the treatment of autoimmune disorders. This type of treatment offers the most effective way to inhibit surface LT on pathogenic immune cells, and stem their autoimmune capabilities. Major biotechnology companies such as Genetech and Biogen Idec have already begun creating these antibodies and implementing them in clinical situations. Three such anti-LTα antibodies are Infliximab and Adalimumab, which are anti-LTα monoclonal antibodies, and Entanercept, which was engineered from human type II TNF (tumor necrosis factor) receptors. All of these antibodies were engineered as Rheumatoid Arthritis (RA) therapies, however as was mentioned above, recent research suggests that as LT alpha is implicated in the pathogenesis of many autoimmune diseases. Therefore scientists are exploring other autoimmune diseases in which anti-LT antibodies therapies, such as these could be effect treatments. However, recent studies have found that the anti-LTα antibodies have an impact on autoimmune diseases other than RA, but Entanercept was not. These findings illustrate that the mechanism of pathogenesis in each autoimmune disease is different, and that while LT alpha has been shown to play a part in many different diseases, inhibiting it with antibody therapies may not be effective in some autoimmune diseases. For example, inhibiting the mechanism of Complement Dependent Cytotoxicity(CDC) may prove to be effective in Crohn's Disease, while doing the same thing may in fact be harmful in Wegener’s Granulomatosis. This shows that while LT is a very effective target in many autoimmune diseases, the type of LT being targeted and the mechanism used to target it must be considered based on which autoimmune disease is being treated.