Compositions and methods relating to c5l2

A method of enhancing Th1 and/or Th17 responses by a mammalian T cell, the method comprising contacting the cell with a C5L2 inhibitor.

The method of any of the preceding claims, comprising contacting the cell with a C5L2 inhibitor in vivo by administering the C5L2 inhibitor to a mammalian subject.

The method of any of the preceding claims, comprising contacting the cell with a C5L2 inhibitor in vivo by administering the C5L2 inhibitor to a mammalian subject who may benefit from increased production of IL-17 and/or IFN-γ.

The method of any of the preceding claims, comprising contacting the cell with a C5L2 inhibitor in vivo by administering the C5L2 inhibitor to a mammalian subject who may benefit from increased Th1 and/or Th17 responses.

The method of any of the preceding claims, wherein the mammalian T cell is a human T cell or wherein the mammalian subject is a human subject.

The method of any of the preceding claims, wherein the C5L2 inhibitor comprises an antibody, an engineered non-antibody polypeptide, a peptide, a peptidomimetic, or a small molecule.

The method of any of the preceding claims, wherein the C5L2 inhibitor comprises a variant of C5a, optionally comprising a substitution at position 69 of C5a.

The method of any of the preceding claims, wherein the C5L2 inhibitor comprises a variant of C5a comprising a positively charged amino acid at position 69 (such as arginine), optionally having a deletion of amino acid 74 of C5a, further optionally having deletion or substitution at one or more of positions 71-73 of C5a, further optionally wherein the variant is A8 or A8Delta71-73.

A method of identifying a candidate inhibitor of C5L2, the method comprising contacting a mammalian T cell with a test agent and determining whether the test agent increases production of IL-17, IFN-γ, or both, by the T cell, wherein an agent that increases production of IL-17, IFN-γ, or both, by the T cell, is a candidate inhibitor of C5L2.

A method of identifying an enhancer of Th1 and/or Th17 responses, the method comprising identifying a C5L2 inhibitor.

The method of any of the preceding claims, wherein the C5L2 inhibitor enhances secretion of IL-17, IFN-γ, or both by the mammalian T cell.

A composition comprising an inhibitor of C5L2 for use in performing the method of any the preceding claims, optionally wherein the composition is a pharmaceutical composition.

A method of enhancing production of interleukin-6 (IL-6), interleukin 1 beta (IL-1β), or both by a mammalian T cell or monocyte, the method comprising contacting the cell with a C5L2 inhibitor.

A method of decreasing suppressive activity of a natural regulatory T (nTreg) cell, the method comprising contacting an nTreg cell with an inhibitor of C5L2.

A method of identifying a candidate inhibitor of C5L2, the method comprising contacting a mammalian T cell or monocyte with a test agent and determining whether the test agent increases production of IL-6, IL-1β, or both, by the T cell, wherein an agent that increases production of IL-6, IL-1β, or both, by the T cell or monocyte is a candidate inhibitor of C5L2.

A method of identifying a candidate inhibitor of C5L2, the method comprising contacting a mammalian nTreg cell with a test agent and determining whether the test agent decreases suppressive activity of the nTreg cell, wherein an agent that decreases suppressive activity of the nTreg cell is a candidate inhibitor of C5L2.

A method of inhibiting production of interleukin-17 (IL-17), interferon gamma (IFN-γ), or both, by a mammalian T cell, the method comprising contacting the cell with a C5L2 activator.

A method of inhibiting Th1 and/or Th17 responses by a mammalian T cell, the method comprising contacting the cell with a C5L2 activator.

A method of inhibiting production of interleukin-6 (IL-6), interleukin 1 beta (IL-1β), or both by a mammalian T cell or monocyte, the method comprising contacting the cell with a C5L2 activator.

A method of increasing suppressive activity of a mammalian nTreg cell, the method comprising contacting the cell with a C5L2 activator.

A method of identifying a candidate activator of C5L2, the method comprising contacting a mammalian T cell with a test agent and determining whether the test agent decreases production of IL-17, IFN-γ, or both, by the T cell, wherein an agent that decreases production of IL-17, IFN-γ, or both, by the T cell, is a candidate activator of C5L2.

A method of identifying a candidate activator of C5L2, the method comprising contacting a mammalian T cell with a test agent and determining whether the test agent decreases production of IL-6, IL-1β, or both, by the T cell or monocyte, wherein an agent that decreases production of IL-6, IL-1β, or both, by the T cell or monocyte, is a candidate activator of C5L2.

A method of identifying an inhibitor of Th1 and/or Th17 responses, the method comprising identifying a C5L2 activator.

The method of any of claims 49-78, wherein the C5L2 activator inhibits secretion of IL-17, IFN-γ, or both by the mammalian T cell.

The method of any of the preceding claims, wherein the C5L2 inhibitor or C5L2 activator is physically associated with a clearance reducing moiety, targeting moiety, a cell uptake moiety, a cell-reactive moiety, or a cell membrane binding moiety.

An agent comprising a C5L2 inhibitor or a C5L2 activator physically associated with a clearance reducing moiety, a targeting moiety, a cell uptake moiety, a cell-reactive moiety, or a cell membrane binding moiety, wherein optionally the C5L2 inhibitor or activator is covalently linked to the clearance reducing moiety, targeting moiety, cell uptake moiety, cell-reactive moiety, or cell membrane binding moiety.

A composition comprising a C5L2 inhibitor and a second agent, wherein the second agent is useful for treatment of cancer or an infection.

A composition comprising a C5L2 activator and a second agent, wherein the second agent is useful for treatment of an autoimmune disease or an inflammatory disease.

A method of treating a subject in need of treatment for an IL-6 mediated disease, the method comprising treating the subject with a C5L2 activator.